KR20200047687A - Constrained conditionally activated binding protein - Google Patents

Abstract

The present invention relates to conditional bispecific oriented activated constructs or COBRAs, administered in the form of an active prodrug. Upon exposure to tumor proteases, these constructs are cleaved and activated so that they bind to both tumor target antigens (TTAs) and CD3 and thus recruit T cells expressing CD3 to the tumor, causing treatment.

Description

Constrained conditionally activated binding protein

I. Cross reference to related applications

This application is 35 U.S.C. U.S. filed September 8, 2017 under §119 (e). U.S. Patent Application No. 62 / 555,943, filed on November 15, 2017. Patent application 62 / 586,627, and U.S. filed on November 16, 2017. Priority is claimed in patent application 62 / 587,318, all of which are expressly incorporated herein by reference in their entirety.

II. References to "List of Sequences", Tables, or Appendixes of the list of computer programs submitted on compact disc

The sequence listing contained in a file named “118459-5005_ST25.txt” and contained in a file having a size of 984 kilobytes was electronically submitted with the present application via the EFS-web, and the contents of the txt file are incorporated herein by reference in their entirety. .

III. Background of invention

Selective destruction of individual cells or specific cell types in various clinical settings is often desirable. For example, the main purpose of cancer therapy is to specifically destroy tumor cells, leaving healthy cells and tissues as intact and intact as possible. One such method is to induce an immune response to a tumor, such that immune effector cells, such as natural killer (NK) cells or cytotoxic T lymphocytes (CTLs), attack and destroy tumor cells.

The use of intact monoclonal antibodies (mAbs) that provide good binding specificity and affinity for tumor-associated antigens has been successfully applied in the field of cancer treatment and diagnosis. However, the large size of intact mAbs, their poor biodistribution, low efficacy and long persistence in the blood puddle limited their clinical application. For example, intact antibodies can exhibit specific accumulation within the tumor zone. In biodistribution studies, heterogeneous antibody distribution with major accumulation in the peripheral region is observed when accurately examining the tumor. Due to tumor necrosis, heterogeneous antigen distribution and increased interstitial tissue pressure, it is not possible for the intact antibody construct to reach the central part of the tumor. In contrast, smaller antibody fragments show rapid tumor localization, penetrate deeper into the tumor, and are also relatively rapidly removed from the bloodstream. However, many antibodies, including scFvs and other constructs, show an “on target / off tumor” effect, where the molecule is active in non-tumor cells and causes side effects, some of which may be toxic. The present invention relates to novel constructs that are selectively activated in the presence of tumor proteases.

IV. Summary of the invention

The present invention provides a number of different protein compositions for the treatment of cancer. Thus, in one aspect, the present invention provides a "Type 2" protein, from N-terminus to C-terminus, comprising: a first single domain antigen binding domain (sdABD) that binds to a human tumor target antigen (TTA) ( sdABD-TTA); b) the first domain linker; c) i) the first variable heavy chain domain comprising vhCDR1, vhCDR2 and vhCDR3; ii) Constrained Uncleavable Linker (CNCL); And iii) a restricted Fv domain comprising a first variable light domain comprising vlCDR1, vlCDR2 and vlCDR3; d) a second domain linker; e) a second sdABD-TTA; f) a cleavable linker (CL); g) i) the first pseudo light chain variable domain; ii) non-cleavable linker (NCL); And iii) a restricted pseudo Fv domain comprising a first pseudo heavy chain variable domain; h) a third domain linker; And i) a third sdABD binding to human serum albumin; Wherein the first variable heavy chain domain and the first variable light chain domain can bind human CD3, but the restricted Fv domain does not bind CD3; The first variable heavy chain domain and the first pseudo variable light chain domain are intramolecularly linked to form an inactive Fv; And the first variable light chain domain and the first pseudo-variable heavy chain domain are intramolecularly linked to form an inactive Fv.

In a further aspect, the present invention provides a "Form 1" protein, from N-terminus to C-terminus, comprising: a) the first sdABD-TTA; b) the first domain linker; c) i) the first variable heavy chain domain comprising vhCDR1, vhCDR2 and vhCDR3; ii) constrained cleavable linker (CCL); And iii) a restricted Fv domain comprising a first variable light domain comprising vlCDR1, vlCDR2 and vlCDR3; d) a second domain linker; e) a second sdABD-TTA; f) a cleavable linker (CL); g) i) the first pseudo light chain variable domain; ii) non-cleavable linker (NCL); And iii) a restricted pseudo Fv domain comprising a first pseudo heavy chain variable domain; h) a third domain linker; And i) a third sdABD binding to human serum albumin; Wherein the first variable heavy chain domain and the first variable light chain domain can bind human CD3, but the restricted Fv domain does not bind CD3; Wherein the first variable heavy chain domain and the first pseudo variable light chain domain are intramolecularly linked to form an inactive Fv; And here, the first variable light chain domain and the first pseudo variable heavy chain domain are intramolecularly linked to form an inactive Fv.

In a further aspect, the present invention provides a "Type 4" protein from N-terminus to C-terminus comprising: a) a single domain antigen binding domain (sdABD) (sdABD) that binds to a human tumor target antigen (TTA). -TTA); b) the first domain linker; c) i) the first variable heavy chain domain comprising vhCDR1, vhCDR2 and vhCDR3; ii) Constrained Uncleavable Linker (CNCL); And iii) a restricted Fv domain comprising a first variable light domain comprising vlCDR1, vlCDR2 and vlCDR3; d) a cleavable linker (CL); e) a second sdABD that binds human serum albumin; f) domain linker; g) i) the first pseudo light chain variable domain; ii) non-cleavable linker (NCL); And iii) a restricted pseudo Fv domain comprising a first pseudo heavy chain variable domain; Wherein the first variable heavy chain domain and the first variable light chain domain can bind human CD3, but the restricted Fv domain does not bind CD3; Wherein the first variable heavy chain domain and the first pseudo variable light chain domain are intramolecularly linked to form an inactive Fv; And here, the first variable light chain domain and the first pseudo variable heavy chain domain are intramolecularly linked to form an inactive Fv.

In a further aspect of the Type 1, Type 2 and Type 4 proteins listed above, the first variable heavy chain domain is the N-terminus of the first variable light chain domain, and the pseudo light chain variable domain is of the pseudo variable heavy chain domain. N-terminal.

In a further aspect for the Type 1, Type 2 and Type 4 proteins listed above, the first variable heavy chain domain is the N-terminus of the first variable light chain domain, and the pseudo variable heavy chain domain is of the pseudo variable light chain domain. N-terminal.

In a further aspect for the Type 1, Type 2 and Type 4 proteins listed above, the first variable light chain domain is the N-terminus of the first variable heavy chain domain, and the pseudo light chain variable domain is of the pseudo variable heavy chain domain. N-terminal.

In a further aspect of the Type 1, Type 2 and Type 4 proteins listed above, the first variable light chain domain is the N-terminus of the first variable heavy chain domain, and the pseudo variable heavy chain domain is of the pseudo variable light chain domain. N-terminal.

In a further aspect, the present invention provides a type 1 and 2 protein having the same first and second TTA.

In a further aspect, the present invention provides type 1 and 2 proteins with different first and second TTAs.

In a further aspect, the present invention provides the type 1, 2 and 4 proteins wherein the first and second TTAs are selected from EGFR, EpCAM, FOLR1 and B7H3. These sequences are SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 25, SEQ ID NO: 29; SEQ ID NO: 33; It can be selected from the group consisting of SEQ ID NO: 37 and SEQ ID NO: 41.

In a further aspect, the present invention provides a type 1, 2 and 4 protein wherein the half-life extending domain has SEQ ID NO: 45.

In a further aspect, the present invention provides that the cleavable linker is MMP2, MMP9, mephrine A, mephrine B, cathepsin S, cathepsin K, cathepsin L, granzyme B, uPA, kallikrein7, matriptase And human protease selected from the group consisting of thrombin.

In a further aspect, the present invention is Pro186, Pro225, Pro226, Pro233, Pro311, Pro312, Pro313, Pro495, Pro246, Pro254, Pro255, Pro256, Pro420, Pro421, Pro432, Pro479, Pro480, Pro187, Pro221, Pro222, Pro223, Provides a protein selected from the group consisting of Pro224, Pro393, Pro394, Pro395, Pro396, Pro429, Pro430 and Pro431.

In a further aspect, the present invention provides nucleic acid encoding a type 1, type 2 or type 4 protein as described herein, as well as expression vectors and host cells comprising the nucleic acid encoding the protein.

In a further aspect, the invention provides a method of making the protein of the invention and a method of treating a patient in need of treatment.

In a further aspect, the present invention provides a composition comprising a “form 3A” pair of prodrug proteins comprising: a) from the N end to the C end, i) the first sdABD-TTA; ii) first domain linker; iii) from N-terminal to C-terminal, 1) variable heavy chain comprising vhCDR1, vhCDR2 and vhCDR3; 2) cleavable linker; And 3) a pseudo Fv domain comprising a first pseudo variable light domain comprising iVLCDR1, iVLCDR2 and iVLCDR3; iv) second domain linker; v) the first protein comprising sdABD-HSA; a) from N-terminus to C-terminus, i) a third sdABD that binds the human tumor target antigen; ii) a third domain linker; iii) from N-terminal to C-terminal, 1) variable light chain comprising VLCDR1, VLCDR2 and VLCDR3; 2) cleavable linker; And 3) a pseudo Fv domain comprising a first pseudo variable heavy chain domain comprising iVHCDR1, iVHCDR2 and iVHCDR3; iv) a fourth domain linker; v) the first second protein comprising sdABD-HSA; Wherein the first variable heavy chain domain and the first variable light chain domain are capable of binding human CD3 when associated; Wherein the first variable heavy chain domain and the first pseudo-variable light chain domain form an inactive Fv in association with the molecule; Wherein the first variable light chain domain and the first pseudo variable heavy chain domain form an inactive Fv in association with the molecule; And wherein the first and third sdABD are SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 25, SEQ ID NO: 29; SEQ ID NO: 33; SEQ ID NO: 37 and SEQ ID NO: 41.

In a further aspect, the present invention provides a composition comprising a “form 3B” pair of prodrug proteins comprising: a) from the N end to the C end, i) the first sdABD-TTA; ii) first domain linker; iii) a second sdABD-TTA; iv) second domain linker; iii) from N-terminal to C-terminal, 1) variable heavy chain comprising vhCDR1, vhCDR2 and vhCDR3; 2) cleavable linker; And 3) a pseudo Fv domain comprising a first pseudo variable light domain comprising iVLCDR1, iVLCDR2 and iVLCDR3; iv) a third domain linker; And v) the first protein comprising sdABD-HSA; a) from the N end to the C end, i) a third sdABD-TTA; ii) a fourth domain linker; iii) fourth sdABD-TTA; iv) fifth domain linker; iii) from N-terminal to C-terminal, 1) variable light chain comprising VLCDR1, VLCDR2 and VLCDR3; 2) cleavable linker; And 3) a pseudo Fv domain comprising a first pseudo variable heavy chain domain comprising iVHCDR1, iVHCDR2 and iVHCDR3; iv) sixth domain linker; v) the first second protein comprising sdABD-HSA; Wherein the first variable heavy chain domain and the first variable light chain domain are capable of binding human CD3 when associated; Wherein the first variable heavy chain domain and the first pseudo-variable light chain domain form an inactive Fv in association with the molecule; And here, the first variable light chain domain and the first pseudo variable heavy chain domain form an inactive Fv in association with the molecule.

In a further aspect, Form 3A and Form 3B proteins have sdABD-HSA having SEQ ID NO: 45.

In a further aspect, Type 3A and Type 3B proteins have sdABD-TTA that binds to TTA selected from EGFR, EpCAM, FOLR1 and B7H3. sdABD-TTAs are SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 25, SEQ ID NO: 29; SEQ ID NO: 33; It can be selected from the group consisting of SEQ ID NO: 37 and SEQ ID NO: 41.

In a further aspect, the invention provides a nucleic acid composition comprising a first nucleic acid encoding a first protein member of a prodrug pair and a second nucleic acid encoding a second protein member of these pairs, and an expression vector containing these nucleic acids. And host cells.

V. Brief description of drawings
1 depicts a “Form 1” type of protease activation of the invention, referred to herein as a “constrained, cleavable construct” or “cc construct”. In this embodiment, a representative construct is Pro140: there are ABDs for two TTAs (as depicted in Figure 1, although they may differ as described herein, they are both the same). Upon cleavage, the prodrug construct is divided into three components, one component containing the α-TTA domain linked to the active VH of αCD3 via a domain linker, and the second component to the active VL of αCD3 via a domain linker. Contain a linked α-TTA domain, and the “remaining” fragment contains inactive VH and half-life extending domains linked to VL. These two active variable domains are then freely associated to form a functional anti-CD3 binding domain. It should be noted that in the "Form 1" embodiment, the resulting active ingredient is refrained: in some cases, this ternary has a monovalent bond to CD3, a monovalent bond to the first TTA and a trivalent bond to the second TTA Although it can be specific, bispecific binding proteins are produced by monovalent binding to CD3 and bivalent binding to TTA. 1 also shows an anti-human serum albumin (HSA) domain as a half-life extension domain, sdABD as defined herein in many embodiments, but as discussed herein, this is an optional and / or other half-life extension domain Can be replaced by; Additionally, the half-life extending domain may also be N-terminal or internal of the construct. 1 also has the VH and VL of Fv and the iVH and iVL of the caustic Fv in a specific order, e.g., from the N-terminus to the C-terminus, VH-linker-VL (and iVL-linker-iVH), although those skilled in the art As recognized by, they can be reversed (VL-linker-VH and iVH-linker-iVL). Alternatively, one of these Fvs may be in one orientation, and the other may be in another orientation, but as shown herein, the expression of the protein in one orientation is surprisingly higher than the other orientation.
FIG. 2 is a protease of the invention, referred to herein as a “constrained, non-cleavable construct”, or “CNCL construct”, and sometimes also referred to herein as a “dimerization construct” as discussed herein. Describes the "form 2" type of activation. These constructs do not isomerize as discussed herein. Upon cleavage, the two prodrug constructs are two half-life extending domains (in this case, linked to four components: two false domains, depending on the length of the linker and an inactivating mutation, which may or may not be autocorrelated). SdABDs for HSA), and two self-assembled with dimeric active moieties containing four anti-TTA domains, all of which may be identical, or two are identical and the other two are different. It is divided into active moieties. It should be noted that in the "Type 2" embodiment, the resulting active ingredient is hexavalent: although in some cases, hexavalent has a bivalent bond to CD3, a bivalent bond to the first TTA and a bispecific bond to the second TTA. Although it can be a sieve, bispecific binding proteins are produced by bivalent binding to CD3 and tetravalent binding to TTA. 2 also shows an anti-human serum albumin (HSA) domain as a half-life extension domain, sdABD as defined herein in many embodiments, but as discussed herein, this is an optional and / or other half-life extension domain Can be replaced by; Additionally, the half-life extending domain may also be N-terminal or internal of the construct. Figure 2 also has VH and VL of Fv and iVH and iVL of pseudo Fv in a specific order, e.g., from N-terminus to C-terminus, VH-linker-VL (and iVL-linker-iVH), although those skilled in the art As recognized by, they can be reversed (VL-linker-VH and iVH-linker-iVL). Alternatively, one of these Fvs may be in one orientation, and the other may be in another orientation, but as shown herein, the expression of the protein in one orientation is surprisingly higher than the other orientation.
3A-3B are also two different polypeptide chains that together make up the MCE therapeutic agent as discussed further herein, sometimes as a “hemi-construct” or “hemi-COBRA ™” as outlined herein. Describes the type of "form 3" of the construct, referred to. In this embodiment, these constructs are delivered in pairs, whereby inactive anti-CD3 Fv domains are caused by self-assembly in preliminary family molecules. Upon cleavage, the inactive variable domain is released, and the two active variable domains are then assembled intermolecularly to form an active anti-CD3 binding domain. These two sdABD-TTAs bind to the corresponding receptors on the tumor cell surface, and cleavage is acted by the protease. This allows intermolecular assembly because these molecules are physically held in place, favoring the assembly of active anti-CD3 domains. As described above for Forms 1 and 2, in this embodiment, the N-to-C-terminal sequence of the variable domain can also be reversed or mixed. Moreover, sdABD (HSA) can be either the N-terminus or the C-terminus of each hemi- construct. Pro16 has sdABD (HSA) at the C terminus, and Pro17 has it at the N terminus (see Pro19, SEQ ID NO: XX has sdABD (HSA) at the C terminus). FIG. 3A shows Form 3 constructs with a single sdABD-TTA domain per hemi-composition, and FIG. 3B shows two sdABD-TTAs per hemi-composition, in the “dual targeting” or “hetero-targeting” format. It shows the format 3 constructs. Note that FIG. 3B uses FOLR1 and EGFR as two TTAs, but other combinations as outlined herein can also be used.
Figure 4 depicts the "Form 4" type of construct, similar to the "Form 2" construct, but with only a single sdABD-TTA. The figure shows sdABD-TTA for EGFR, however, as recognized by one of skill in the art, other TTAs can also be used. Upon cleavage, the prodrug construct has two components: in the presence of a second active moiety from two cleaved molecules: a half-life extending domain (in this case, sdABDs for HSA) linked to a caustic Fv. It is divided into active moieties that self-assemble into dimeric active moieties containing the -TTA domain. It should be noted that in the "Form 4" embodiment, the resulting active ingredient is Saga: bispecific binding proteins to CD3 and bivalent binding to TTA are made. 4 also shows an anti-human serum albumin (HSA) domain as a half-life extending domain, sdABD (1/2) as defined herein in many embodiments, but as discussed herein, this is optional and / or Or may be replaced by another half-life extending domain; Additionally, the half-life extending domain may also be N-terminal or internal of the construct. FIG. 4 also has the VH and VL of Fv and the iVH and iVL of the caustic Fv in a specific order, e.g., from N-terminus to C-terminus, VH-linker-VL (and iVL-linker-iVH), although those skilled in the art As recognized by, they can be reversed (VL-linker-VH and iVH-linker-iVL). Alternatively, one of these Fvs may be in one orientation, and the other may be in another orientation, but as shown herein, the expression of the protein in one orientation is surprisingly higher than the other orientation.
5A-5G depict multiple sequences of the invention. In the case of antigen binding domains, CDRs are underlined. As more fully outlined herein, these domains can be assembled in a wide variety of shapes in the present invention, including "form 1", "form 2", "form 3" and "form 4" orientations. Interestingly, SEQ ID NO: 90 is cleaved by MMP9 slightly faster than SEQ ID NOs: 75 and 76, and SEQ ID NO: 91 is cleaved slower than SEQ ID NOs: 75 and 76.
6A-6B depict a number of suitable protease cleavage sites. As recognized by those skilled in the art, these cleavage sites can be used as cleavable linkers. In some embodiments, for example, when a more flexible cleavable linker is required, there may be additional amino acids (generally glycine and serine) either or both of the N and C ends of these cleavage sites.
7A-7D depict some data associated with a “Type 3” or “Hemi-COBRA ™” structure. This cooperatively binds CD3 after cleavage by the type 3 construct with a protease (in this case the EK protease, although any protease cleavage sites outlined herein and depicted in FIGS. 5 and 6 can be used). And, as shown by the sandwich FACS analysis, demonstrates creating a CD3 binding site.
8A-8D show that protease cleavage cooperatively activates T-cell killing of EGFR + target cells with complementary hemi-COBRA ™ pairs. 8A and 8B show that constructs cleaved separately, but with different concentrations of protease, do not affect target cell viability. However, Figure 8c shows that in combination, in the presence of protease, the target cell viability is significantly reduced. 8D shows the general mechanism.
9 shows some non-target controls for use in assays to test the efficacy of Form 1 constructs.
10A-10F show that the production of active CD3 binding domains is dependent on target binding of both “arms”, eg, the sdABD-TTA domain (one of which is present in each of the two constructs). The TDCC assay was performed as described in the Examples.
11 shows a schematic diagram of a suitable hemi-COBRA ™ pair. “Mep” refers to the mephrine protease cleavage site, “His-6” is a tag as more fully discussed herein, ST14 is the Matriptase protease cleavage site, and “Thb” is the thrombin protease cleavage site. .
12A-12C show TDCC data associated with the construct of FIG. 11. FIG. 12A shows that the addition of a pre-cleaved hemi-COBRA pair causes an effect in OvCAR8 cells, FIG. 12B shows that the addition of a pre-cleaved hemi-COBRA pair causes an effect on HCT116 cells, and 12C shows that the addition of a pre-cleaved hemi-COBRA pair induces an effect on LoVo cells, all of which are cancer cell lines.
13A-13B show that the MMP9 linker is stable in vivo. NSG mice were administered a single intravenous bolus injection dose of either Pro40 (MMP9 cleavable) or Pro74 (noncleatable) through the tail vein at a dose level of 0.5 mg / kg. Dosing solutions for each compound were prepared in 25 mM citric acid, 75-mM L-arginine, 75 mM NaCl and 4% sucrose pH 7.0 carrier. Two blood samples were collected from each animal at preselected time points, one sample collected by orbital bleeding or mandibular bleeding at the start of the study, and the other sample collected by cardiac puncture at the time of termination. Time points for blood collection were 0.083, 1, 6, 24, 72 and 168 hours. Plasma was prepared from each individual blood sample using a K ₂ EDTA tube. Concentrations were determined using an MSD assay with MAb specific for anti-HSA sdABD, and detected with the EGFR extracellular domain.
FIG. 14 depicts a schematic diagram of the type 3A Hemi-COBRA ™ construct used in the experiment depicted in FIG. 15. Pro51 is a positive control, since it is “always on” to form an active anti-CD3 Fv. Pro98 is a negative control because its sdABD is directed against egg lysozyme that is not expressed by the tumor. Pro77 and Pro53 are prodrug type 3A pairs using sdABDs and MMP9 cleavage sites for EGFR. Pro74 and Pro72 are negative control type 3A pairs because they do not have cleavage sites.
15 shows that the Type 1 construct acts to regress tumors in vivo when using two different tumor cell lines implanted into mice using the protocol in the Examples. Antitumor activity with hemi-COBRA constructs (Pro77 and Pro53) relied on the inclusion of both anti-EGFR sdABDs and MMP9 cleavable linkers, along with active anti-CD3 Fv.
FIG. 16 depicts a schematic diagram of a full-length construct with two pseudo Fv domains in a next generation format and a cleavable region between them, as described generally in US 2018/0134789, incorporated herein by reference. However, as shown in the figure below, these first generation full-length constructs do not show very good condition limitations because they can isomerize to form both active and inactive constructs.
FIG. 17 shows that the Form 3A construct pair substantially shows better condition limitations than the Pro100 first generation full length construct.
18 depicts an additional first generation battlefield construct examined in FIG. 19.
FIG. 19 shows that the first generation constructs show high activity even in unopened format, eg poor condition limitation.
20 shows that the first generation full-length construct shows two monomer peaks in analytical SEC.
FIG. 21 shows a phylogenetic diagram of the causes of uncleaved activity, which is caused by isomerization of the full-length first-generation construct in two conformations: one conformation that is inactive because there is no active anti-CD3 Fv formed ("divalent scFv "), And in the absence of a protease it forms another conformation (a shape of the" single chain diabody "type). Reference: PEDS 23 (8): 667-677 (2010).
22 depicts the results of a TDCC assay run with a first generation single chain construct for 2 days at 37C. These results demonstrate that unopened constructs show strong killing. These results led to the calculation of Form 1 constructs.
23A-23G show the Form 1 construct used in the present invention. As recognized by those skilled in the art and described herein, these are depicted as sdABD-EGFR targeting moieties, although sdABDs for other TTAs may be used.
FIG. 24 shows that Form 1 construct (Pro140 in this case) forms a single isomer that is stable at 37C.
25 depicts that Form 1 constructs have very low binding to human CD3 in the uncleaved form when measured by Octet assay. The top line is Pro120 maintained for 3 days at 4C or 37C, the middle line is Pro51 (positive control), and the bottom line is Pro140.
FIG. 26 similarly depicts that Form 1 constructs have very low TDCC activity in the uncleaved form.
FIG. 27 depicts a specific Type 1 construct, Pro140, used in an in vivo assay, using sdABD-EGFR and MMP9 cleavage sites as targeting moieties.
28A-28B depict tumor regression using Form 1 constructs.
29 depicts that due to cleavage sites in constrained Fv, several different fragments: partially cleaved fragments and fully cleaved fragments can be produced. Surprisingly, the partially cleaved form is more active than the fully cleaved form, resulting in the output of Form 2.
30 shows a number of Type 2 phylogenetic diagrams, all of which utilize the sdABD-EGFR targeting domain, although sdABDs for other TTAs can be used, as outlined herein and listed in the sequence. Pro51 and Pro201 are positive controls (in the active "hemi" shape), and Pro214 is a full-length negative control, since there is no cleavage site.
FIG. 31 depicts the TDCC activity of Form 2 construct Pro187 using the mephrine cleavage site. In the TDCC assay, Pro187 was 1200 times more active when pre-cracked was added than when uncracked was added. The pre-cleaved Pro187 showed activity entering between the positive controls Pro51 and Pro201. Unopened Pro187 showed similar activity to Pro214, which does not contain a protease cleavable linker.
FIG. 32 shows TDCC activity of Form 2 construct Pro186 using MMP9 cleavage site. In the TDCC assay, Pro186 was 18 times more active when pre-cracked was added than when uncracked was added. The pre-cleaved Pro186 showed activity entering between the positive controls Pro51 and Pro201. Uncleaved Pro186 showed higher activity than Pro214, which does not contain a protease cleavable linker.
Figure 33 depicts that the Pro186 construct binds cells with different levels of EGFR receptors, CHO cells do not express EGFR on the cell surface. Pro186 saturates cells expressing different levels of EGFR at similar COBRA concentrations.
FIG. 34 depicts a phylogenetic diagram of Form 2 constructs used in the in vivo study of FIG. 35, all of which utilize the sdABD-EGFR targeting domain.
35 shows that Form 2 Construct Pro186 is highly effective at both concentrations and is superior to Form 1 Construct Pro140 at lower concentrations.
FIG. 36 depicts multiple Type 2 constructs based on Pro186 but with different protease cleavage sites. Although all of these constructs utilize sdABD-EGFRs for both targeting domains, other sdABDs for different TTAs can be used, and can be the same or different. In other words, both homo-targeting (both targeting sdABDs for the same TTA) or hetero-targeting (one targeting the first TTA and the other targeting sdABD for different TTAs) can be done.
37 depicts a phylogenetic tree for different type 2 constructs with different linker lengths between Fv domains. Although others can be used as outlined herein, they are shown using the MMP9 cleavage site. Similarly, all of these constructs utilize sdABD-EGFRs for both targeting domains, but other sdABDs for different TTAs may be used, and may be the same or different.
Figure 38 can vary linker length for caustic Fvs, e.g., type 2 constructs with shorter linkers between active Fvs ("short active") and longer linkers between caustic Fvs ("long inactive") It is shown that it exhibits similar activity to constructs with "short activity" and "short activity". Thus, limiting the condition of the COBRA construct does not depend on both the restricted activity and the inactive scFv linker; As long as one of these is constrained, single chain diabody folding appears to be preferred over scFv folding.
Figure 39 can vary linker length for active Fv, e.g., type 2 constructs with "long active" and "short inactive" behave similarly to "short active" and "short inactive" constructs Shows that. Thus, limiting the condition of the COBRA construct does not depend on both the restricted activity and the inactive scFv linker; As long as one of these is constrained, single chain diabody folding appears to be preferred over scFv folding.
40A-40C show a schematic diagram for a number of different constructs. Pro188 is a format 1 construct similar to Pro140, with the exception of a long linker (16mer) in caustic Fv. Pro189 and Pro190 (Form 2 constructs) are similar to Pro186 and Pro187, except for the long linker (16mer) in the pseudo Fv domain. Pro191 and Pro192 (which are also Type 2 constructs) are similar to Pro189 and Pro190, except that they have additional cleavage sites upstream of sdABD (1/2). Pro193 (Type 4) has a single EGFR targeting domain, iVH and iVL rearranged in reversed order, and an additional cleavage site upstream of sdABD (1/2). Pro195 is a type 2 construct similar to Pro186, with targeting domains that bind the same TTA, EGFR, but different epitopes. Pro196, Pro197 and Pro198 are Type 2 constructs with rearranged variable domains.
Figure 41 depicts the fact that different sdABD clones directed towards human FOLR1 show differential killing. Pro22 type constructs that bind human FOLR1 (Pro51 with FLAG sequence instead of NCL) were compared to Pro22-EGFR constructs for multiple cell line families.
FIG. 42 is a Pro201 positive control with sdABD-EGFR2 (two molecules forming two active Fvs for CD3 intermolecularly), and two type 2 test articles, h77.2 Pro311 and h59.3 using hdABD Depicts a schematic for four sdABD-FOLR1 constructs, including the use of Pro312 with sdABD as well as two negative controls, Pro299 with h77.2 sdABD and Pro303 with h59.3 sdABD.
43 depicts a phylogenetic diagram of Form 2 constructs for FOLR / MMP9 in vivo design.
44 shows the potency of the Pro312 construct in vivo, and shows that an MMP9 cleavable linker is required for anti-tumor activity.
Figure 45 uses the positive control Pro244 (sdABD-B7H3 (hF7) (two molecules form two active Fvs against CD3 intermolecularly), and two Form 2 test articles, Form 2 construct Pro225 and Some types of phylogenetic tree with sdABDs for human B7H3 (sdABD-B7H3) are depicted, including Pro295, a negative control lacking the cleavage site.
46 shows that Pro225 has a larger condition limit compared to control, Pro295.
FIG. 47 shows that Pro373, a type 2 construct using a mephrine linker, shows greater condition limitation compared to Pro295.
48 depicts multiple sdABD-B7H3 (using hF12 sequences) constructs, Pro51 positive control using sdABD-EGFR, Pro244 positive control using sdABD-hF12 B7H3, Pro construct, test construct Pro226, and no cleavage site. The negative control Pro296 is shown.
49 depicts good condition limitation of Pro226 construct in TDCC assay.
50 shows humanization of sdABDs for human EpCAM.
Figure 51 shows the phylogenetic tree of various types: Pro22hVIB13 and Pro205 are positive controls, Pro199 is Type 2 construct, and Pro175 is negative controls.
Figure 52 shows TDCC activity of the sdABD-EpCAM construct, showing good conditional restriction.
53A-53B show the TDCC activity of the sdABD-EpCAM Pro199 construct showing good condition limitation in HT29 and LoVo cell models.
Figures 54A-54B show the TDCC activity of the sdABD-EpCAM Pro200 construct, showing good condition limitation in HT29 and LoVo cell models.
FIG. 55 shows a schematic diagram of Pro255 using two different sdABD-TTA: one for EGFR (sdABD-EGFR) and the other for EpCAM (sdABD-EpCAM) compared to Pro199 with dual EpCAM sdABDs. . These are sometimes referred to herein as “hetero-targeting” constructs (in this case, Form 2 constructs).
56 shows that the Pro255 dual targeting molecule with MMP9 cleavage site shows good conditional restriction.
57A-57D show the results of experiments in three different cell types. First, Raji transfectants with similar expression levels of EpCAM, EGFR and EpCAM + EGFR were created (data not shown). Subsequently, Pro255 targeting both EpCAM and EGFR was tested in a TDCC assay using each cell type. 57A shows the parental Raji line that does not express any receptor. 57B shows the condition limitations in the EpCAM line. 57C shows the condition limitation in the EGRF line. 57D depicts conditional restriction in the EpCAM / EGFR line.
FIG. 58 depicts a schematic diagram of Form 4 construct Pro258.
59A-59B show that Pro258 is conditional in both FBS and human serum. Conditional limitations of the MMP9 linker are underestimated due to MMP9 activity during culture. Interestingly, Pro51 TDCC activity is inhibited by HSA binding, whereas Pro258 TDCC activity is similar to Pro51 in the presence of HSA. Finally, the Pro258 condition limit is enhanced by 6X in the presence of HSA.
60A-60C depict cleavage of MMP9 substrates by different MMPs.
61A-61B illustrate exemplary constructs and some of their formats.
62A-62U depict multiple sequences of the invention, although many additional sequences are also found in the sequence listing. CDRs are underlined and bold, linkers are double underlined (cleavable linkers are italic and double underlined), and domain separation is indicated by "/". All His6 tags are arbitrary because they can be used to reduce immunogenicity in humans as well as be purified tags.

VI. Detailed description of the invention

A. Introduction

The present invention relates to methods of reducing toxicity and side effects of bispecific antibodies (including antibody-like functional proteins) that bind important physiological targets, such as CD3 and tumor antigens. Many antigen binding proteins, such as antibodies, can have significant off-target side effects and, therefore, in order to prevent off-target interaction, it is necessary to activate the binding ability of the therapeutic molecule only in the vicinity of diseased tissue. Accordingly, the present invention relates to multivalent conditionally effective ("MCE") proteins with multiple functional protein domains. Generally, one of these domains is an antigen binding domain (ABD) that will bind to a target tumor antigen (TTA), and the other is an ABD that will bind a T-cell antigen, such as CD3, under certain conditions. Additionally, the MCE protein also includes one or more protease cleavage sites. In other words, therapeutic molecules are made in a “prodrug” -like format, where the CD3 binding domain is inactive until exposed to the tumor environment. The tumor environment contains proteases such that upon exposure to the protease, the prodrug cleaves and becomes active.

This generally includes proteins comprising a “pseudo” variable heavy chain domain and a “pseudo” variable light chain domain directed towards a T-cell antigen, such as CD3, that inhibits the CD3 Fvs of the MCE in an inactive form, as discussed herein. By using it is achieved herein. Since TTA targets MCE to the vicinity of the tumor, MCE is thus exposed to proteases. Upon cleavage, the active variable heavy chain domain and active light chain domain can now collide to form one or more active ABDs against CD3, and thus recruit T cells to the tumor and trigger treatment.

Generally, the CD3 binding domain (“Fv”) is in a restricted form, where the linker between the active variable heavy chain domain and the active variable light chain domain that traditionally forms Fv allows these two active variable domains to bind each other. Too short to do; This is referred to as the "constrained linker"; These can be constrained and cleavable (as used in CCL, Form 1), or constrained and non-cleavable (as used in CNCL, Form 2). More precisely, in the form of a prodrug (eg, unopened), the prodrug polypeptide also includes a “pseudo Fv domain”. Caustic Fv domains include standard framework regions, but variable heavy and light chain domains with “inactive” or “inactive” CDRs. The pseudo Fv domain also has a linker constrained between the inactive variable heavy chain and inactive variable light chain domains. Because neither of the Fv and pseudo Fv domains can self-assemble due to steric constraints, due to the affinity of each framework region, there is an intramolecular assembly that matches aVL with iVH and aVH with iVL. However, due to the "inactive" CDRs of the pseudo domain, the resulting ABDs will not bind CD3 and thus will prevent off-target toxicity. However, in the tumor or in the presence of a protease in the vicinity of the tumor, the prodrug construct allows the pseudo-Fv domain to be released from the surface, thus allowing the "real" variable heavy and variable light chain domains to be intermolecularly linked (eg For example, two cleaved constructs are allowed to merge), thus triggering active CD3 binding and resulting tumor efficacy. These constructs are collectively referred to herein as conditional bispecific oriented activated constructs, or "COBRAs ™". The stability of the intramolecular assembly is found here by condition limiting experiments, where in the absence of a protease, the uncleaved construct has no activity (eg, no active CD3 binding domain is formed).

Interestingly, for convenience of explanation, although all of these constructs are referred to herein as "restricted", further studies have shown that even if one of the Fv domains is not restricted, for example, one of these domains is longer, a flexible linker Although it may have, it shows that intramolecular assembly is preferred. In other words, as shown in Figures 36, 37, and 38, if either one of the Fv domains, having an active VL and VH, or having a pseudo Fv domain is constrained, intramolecular assembly It still occurs (eg, unopened constructs are inactive in the absence of protease cleavage). However, in the current system, when both linkers are restricted, the protein has better expression. However, as will be appreciated by those skilled in the art, any Form 1, Form 2 or Form 4 construct herein can have one of these Fv domains with a “unconstrained” or “flexible” linker. For convenience of reference, the construct is shown in a format in which both Fv domains are constrained.

The constructs and forms of the present invention are modifications relative to the invention described in WO2017 / 156178, which is hereby expressly incorporated by reference in its entirety. As shown in Figure 20, previous constructs areomerized due to the presence of two sets of VH and VL domains in a single polypeptide, thereby having the ability to form both a scFv and a single chain diabody. Even after purification of each isoform, the lice construct can still reach equilibrium with the diabody isoform. Since single chain diabodies have the ability to bind CD3 in the absence of protease cleavage, the usefulness of the construct is diminished.

To address this problem, the present invention provides four distinct types of constructs to achieve this conditional activation. Prodrug activation can occur in one of four general ways, as shown generally in the figure. In FIG. 1, the “Type 1” mechanism is shown. In this embodiment, the prodrug construct has two cleavage sites: one cleavage site between the VH and vl domains of the restricted Fv (so these two variable domains are freely associated), and caustic from the prodrug construct. The second cleavage site (thus the T cell to the tumor site) from the site that releases the Fv domain, leaving two related molecules due to innate self-assembly of the variable heavy and variable light chain domains, each having an antigen binding domain to the tumor antigen. Allows mobilization).

In an alternative embodiment, the prodrug construct is depicted in Figure 2, "Form 2" mechanism. In this embodiment, the domain linker between the active variable heavy chain and the active light chain is a restricted but non-cleavable linker ("CNCL"). In this prodrug form, the inactive VH and VL of the constrained caustic Fv domain are complementary to the VH and VL of the constrained Fv domain, thus lacking CD3 binding. However, once cleavage occurs in the tumor environment, two different activated proteins, each comprising an active variable heavy and light chain domain, are associated to form two anti-CD3 binding domains.

In addition to the “single chain protein” COBRA format discussed above, in which all components are nested in a single amino acid sequence, there are also constructs “hemi-COBRAs” that depend on two proteins, which are paired as shown in FIG. 3. Act as In this embodiment, each protein has one active and one inactive variable domain separated by a protease cleavage site. Each molecule contains a TTA binding domain such that when these molecules bind to TTA and are exposed to tumor proteases, the inactive domains are cleaved and the two active variable domains self-assemble to form an anti-CD3 binding domain.

In addition, the present invention also provides a "Form 4" construct as depicted in FIG. 4. These are similar to the "Type 2" design, except that a single ABD for TTA is used, as described further below, two of the prodrug molecules upon cleavage contain two active anti-CD3 domains. Saga, bispecific constructs are now formed.

Thus, the forms and constructs of the present invention find use in the treatment of diseases.

B. Definition

In order to make the application more fully understood, several definitions are set out below. This definition is meant to encompass grammatical equivalents.

As used herein, “amino acid” and “amino acid identity” are meant to be one of 20 naturally occurring amino acids or any non-natural analogs that may exist at a particular, defined position. In many embodiments, “amino acid” means one of 20 naturally occurring amino acids. "Protein" is meant herein to be at least two covalently attached amino acids, which include proteins, polypeptides, oligopeptides and peptides.

“Amino acid modification” is meant herein to be an amino acid substitution, insertion and / or deletion in a polypeptide sequence or a modification to a moiety chemically linked to a protein. For example, the modification can be a modified carbohydrate or PEG structure attached to the protein. For clarity, unless otherwise stated, amino acid modifications are always modifications to amino acids encoded by DNA, such as 20 amino acids with codons in DNA and RNA. Preferred amino acid modifications herein are substitutions.

“Amino acid substitution” or “substitution” is meant herein to be the replacement of an amino acid for a different amino acid at a particular position in the parent polypeptide sequence. In particular, in some embodiments, the substitution is a substitution with an amino acid that does not occur naturally at a particular position, does not occur naturally within an organism, or does not occur naturally in any organism. For clarity, a protein processed to change the nucleic acid coding sequence but not the starting amino acid (e.g., replacing CGG (encoding arginine) with CGA (still encoding arginine) to increase the level of host organism expression) Is not "amino acid substitution"; In other words, despite the creation of a new gene encoding the same protein, if the protein has the same amino acid at the specific location where it starts, it is not an amino acid substitution.

As used herein, “amino acid insertion” or “insertion” is meant to be the addition of an amino acid sequence at a particular position within the parent polypeptide sequence.

As used herein, “amino acid deletion” or “deletion” is meant to be the removal of the amino acid sequence at a particular position within the parent polypeptide sequence.

Polypeptides of the invention specifically bind to CD3 and target tumor antigens (TTAs), such as target cell receptors, as outlined herein. “Specific binding” or “specifically binds” or “specific” to a specific antigen or epitope means binding that is measurably different from a non-specific interaction. Specific binding can be measured, for example, by determining the binding of a molecule as compared to that of a control molecule, which is a molecule of similar structure, which generally does not have binding activity. For example, specific binding can be determined by competition with a target-like control molecule.

Specific binding to a specific antigen or epitope is, for example, at least about 10 ^-4 M, at least about 10 ^-5 M, at least about 10 ^-6 M, at least about 10 ^-7 M, at least about 10 ^-8 M, at least About 10 ^-9 M, alternatively at least about 10 ^-10 M, at least about 10 ^-11 M, at least about 10 ^-12 M, or more, can be exhibited by an antibody having a KD against an antigen or epitope, where KD Refers to the dissociation rate of a specific antibody-antigen interaction. Typically, an antibody that specifically binds an antigen is 20-fold, 50-fold, 100-fold, 500-fold, 1000-fold, 5,000-fold, 10,000-fold or more relative to the control molecule compared to the antigen or epitope You will have an ideal KD.

In addition, specific binding to a specific antigen or epitope, e.g., at least 20-fold, 50-fold, 100-fold, 500-fold, 1000-fold, 5,000-fold, 10,000-fold for the epitope relative to the control Or antibodies with KA or Ka to more antigens or epitopes, where KA or Ka refers to the association rate of a particular antibody-antigen interaction. Binding affinity is generally measured using a Biacore assay or Octet as known in the art.

As used herein, “parent polypeptide” or “precursor polypeptide” (including Fc parent or precursor) is meant to be a polypeptide that is subsequently modified to yield a variant. The parent polypeptide can be a naturally occurring polypeptide, or a variant or engineered version of a naturally occurring polypeptide. The parent polypeptide may refer to the polypeptide itself, a composition comprising the parent polypeptide, or an amino acid sequence encoding it. Thus, as used herein, “parent Fc polypeptide” is meant to be an unmodified Fc polypeptide that is modified to yield a variant, and as used herein, “parent antibody” yields a variant antibody. It is meant to be an unmodified antibody that is modified to.

As used herein, “position” is meant to be a position within the sequence of a protein. The positions can be numbered sequentially or according to an established format, such as the EU index for antibody numbering.

As used herein, “target antigen” is meant to be a molecule that is specifically bound by the variable region of a given antibody. The target antigen can be a protein, carbohydrate, lipid, or other chemical compound. Various suitable exemplary target antigens are described herein.

As used herein, “target cell” is meant to be a cell that expresses a target antigen. Generally, for the present invention, target cells are tumor cells expressing TTAs, or T cells expressing a CD3 antigen.

As used herein, “Fv” or “Fv domain” or “Fv region” is generally meant to be a polypeptide comprising the VL and VH domains of an antigen binding domain from an antibody. Fv domains typically form "antigen binding domains" or "ABDs" as discussed herein, if they contain active VH and VL domains (although in some cases, active ABD is not formed prior to cleavage) , Although Fv containing a constrained linker is used). As discussed below, Fv domains can be organized in a variety of ways in the present invention, and can be “active” or “inactive” in, for example, scFv format, constrained Fv format, pseudo Fv format, and the like. In the present invention, in some cases, the Fv domain is composed of VH and VL domains on a single polypeptide chain, for example, as shown in FIGS. 1 and 2, but is understood to have a linker constrained so that intramolecular ABD cannot be formed. Should be. In these embodiments, two active ABDs are formed after cleavage. In some cases, the Fv domain consists of VH and VL domains, one of which is inactive such that intermolecular ABD is formed only after cleavage. As discussed below, Fv domains can be organized in a variety of ways in the present invention, and can be “active” or “inactive”, such as in scFv format, constrained Fv format, pseudo Fv format, and the like. In addition, as discussed herein, Fv domains containing VH and VL can be / or form ABDs, and other ABDs that do not contain VH and VL domains can be formed using sdABDs.

A “variable domain” herein is a region of an immunoglobulin comprising one or more Ig domains that are actually encoded by one of the Vκ, Vλ and / or VH genes, each of which constitutes a kappa, lambda and heavy chain immunoglobulin locus. It is meant to be. In some instances, a single variable domain, such as sdFv (also referred to herein as sdABD) can be used.

In embodiments utilizing both variable heavy (VH) and variable light (VL) domains, each VH and VL is three hypervariable regions ("complementarity determining regions," arranged in the following order from amino to carboxy terminus: CDRs ”) and four“ framework regions ”, or“ FRs ”: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. Thus, the VH domain has the structure vhFR1-vhCDR1-vhFR2-vhCDR2-vhFR3-vhCDR3-vhFR4, and the VL domain has the structure vlFR1-vlCDR1-vlFR2-vlCDR2-vlFR3-vlCDR3-vlFR4. As described more fully herein, the vhFR region and vlFR region are self-assembled to form the Fv domain. Generally, in the prodrug form of the present invention, there are “restricted Fv domains” in which the VH and VL domains are not self-correlated, and “pseudo Fv domains” in which CDRs do not form an antigen binding domain when autocorrelated. .

Hypervariable regions confer antigen binding specificity, and generally, approximately amino acid residues 24-34 (LCDR1; “L” denotes light chain), 50-56 (LCDR2) and 89-97 (LCDR3) within the light chain variable region ), And approximately 31-35B within the heavy chain variable region (HCDR1; “H” denotes heavy chain), 50-65 (HCDR2) and 95-102 (HCDR3) amino acid residues: Kabat et al., SEQUENCES OF PROTEINS OF IMMUNOLOGICAL INTEREST, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991) and / or hypervariable loops in the light chain variable region (e.g., residues 26-32 (LCDR1), 50-52 (LCDR2) and 91-96 (LCDR3), and 26-32 (HCDR1) in the heavy chain variable region ), 53-55 (HCDR2) and 96-101 (HCDR3); Chothia and Lesk (1987) J. Mol. Biol. 196: 901-917. Specific CDRs of the invention are described below. do.

As will be appreciated by those skilled in the art, the exact numbering and placement of these CDRs can be different between different numbering systems. However, it should be understood that the initiation of variable heavy and / or variable light chain sequences includes the initiation of associated (natural) CDRs. Thus, the initiation of each variable heavy chain region is the initiation of vhCDRs (eg, vhCDR1, vhCDR2 and vhCDR3), and the initiation of each variable light chain region is the initiation of vlCDRs (eg, vlCDR1, vlCDR2 and vlCDR3).

A useful comparison of CDR numbering is as follows (Lafranc et al., Dev. Comp. Immunol. 27 (1): 55-77 (2003)):

[Table 1]

Kabat +
Chothia IMGT Kabat AbM Chothia Contact vhCDR1 26-35 27-38 31-35 26-35 26-32 30-35 vhCDR2 50-65 56-65 50-65 50-58 52-56 47-58 vhCDR3 95-102 105-117 95-102 95-102 95-102 93-101 vlCDR1 24-34 27-38 24-34 24-34 24-34 30-36 vlCDR2 50-56 56-65 50-56 50-56 50-56 46-55 vlCDR3 89-97 105-117 89-97 89-97 89-97 89-96

Throughout this specification, the Kabat numbering system and the EU numbering system in the case of the Fc region are generally used when referring to residues within the variable domain (approximately, residues 1-107 of the light chain variable region and residues 1-113 of the heavy chain variable region). (Eg, Kabat et al., Supra (1991)).

The present invention provides a number of different CDR sets. In this case, “complete CDR set” in the context of an anti-CD3 component includes 3 variable light chains and 3 variable heavy chain CDRs, eg, vlCDR1, vlCDR2, vlCDR3, vhCDR1, vhCDR2 and vhCDR3. As will be appreciated by those skilled in the art, each set of CDRs, VH and VL CDRs can bind antigen individually and as a set. For example, in the restricted Fv domain, vhCDRs can, for example, bind CD3, and vlCDRs can bind CD3, but in the restricted form they cannot bind CD3.

In the context of single domain ABD (“sdABD”), such as when used generally to bind a target tumor antigen (TTA) herein, the CDR set is only 3 CDRs; These are sometimes referred to in the art as "VHH" domains.

Each of these CDRs can be part of a larger variable light chain or variable heavy chain domain. In addition, as more fully outlined herein, the variable heavy and variable light chain domains may be on separate polypeptide chains herein or on a single polypeptide chain in the case of scFv sequences, depending on the type and shape of the moiety. .

These CDRs contribute to antigen binding, or more specifically, formation of epitope binding sites. “Epitope” refers to a determinant that interacts with a specific antigen binding site within a variable region known as a paratope. An epitope is a grouping of molecules, such as amino acids or sugar side chains, and usually has specific structural characteristics as well as specific charge characteristics. A single antigen may have more than one epitope.

Epitopes may include amino acid residues directly related to binding (also called epitope immunodominant components) and other amino acid residues not directly related to binding, such as amino acid residues that are effectively blocked by specific antigen binding peptides; In other words, the amino acid residue is within the footprint range of a specific antigen-binding peptide.

Epitopes can be conformational or linear. Conformational epitopes are produced by amino acids spatially juxtaposed from different segments of the linear polypeptide chain. Linear epitopes are those produced by adjacent amino acid residues in a polypeptide chain. Conformational epitopes and non-stereomorphic epitopes can be identified in that binding to the former is lost in the presence of a denaturing solvent, but not in the latter.

Epitopes typically contain at least 3, and more typically, at least 5 or 8-10 amino acids in a unique spatial conformation. Antibodies that recognize the same epitope can be demonstrated in a simple immunoassay demonstrating the ability of an antibody to block binding of another antibody to a target antigen, such as “binning”. As outlined below, the present invention encompasses those competing for binding of the antigen binding domains listed herein with antibodies as well as epitopes bound by the antigen binding domains listed.

The variable heavy and variable light chain domains of the invention can be "active" or "inactive".

As used herein, “inactive VH” (“iVH”) and “inactive VL” (“iVL”) refer to components of the pseudo Fv domain, when these components are matched with their syngeneic VL or VH partners, If it binds to a similar VL or VH that is not "inactive", the "active" VH or "active" VL forms a resultant VH / VL pair that does not specifically bind to the antigen to bind, respectively. Exemplary “inactive VH” and “inactive VL” domains are formed by mutations in the wild-type VH or VL sequence, as outlined more fully below. Exemplary mutations are in CDR1, CDR2 or CDR3 of VH or VL. Exemplary mutations include placing a domain linker in CDR2, thus forming a “inactive VH” or “inactive VL” domain. In contrast, “active VH” or “active VL” is one that is capable of specifically binding a target antigen upon confrontation with a “active” syngeneic partner, ie, VL or VH, respectively. Thus, it should be understood that the pseudo Fv can be a VH / iVL pair, an iVH / VL pair, or an iVH / iVL pair.

In contrast, as used herein, the term "activity" refers to a CD-3 binding domain capable of specifically binding CD-3. These terms are used in two contexts: (a) when referring to a single member (ie, VH or VL) of an Fv binding pair, a sequence that can match a syngeneic partner and specifically bind CD-3. ; And (b) a synergistic pair of sequences capable of specifically binding to CD-3 (ie, VH and VL). Exemplary “active” VH, VL or VH / VL pairs are wild-type or parent sequences.

"CD-x" refers to the differentiation cluster (CD) protein. In exemplary embodiments, CD-x is selected from these CD proteins that have a role in mobilization or activation of T-cells in an individual to whom the polypeptide constructs of the invention have been administered. In an exemplary embodiment, CD-x is CD3, the sequence of which is shown in FIG. 5.

The term “binding domain” in the context of the present invention, (specifically) binds to and / or a specific target epitope or a specific target site on a target molecule (antigen), eg: EGFR and CD-3, respectively. Characterize domains that interact and / or recognize them. The structure and function of the target antigen binding domain (recognizing EGFR) and, preferably, also the structure and / or function of the CD-3 binding domain (recognizing CD3) is an antibody comprising sdABDs, eg full length or full It is based on the structure and / or function of the immunoglobulin molecule. According to the present invention, the target antigen binding domain is generally characterized by the presence of three CDRs that bind the target tumor antigen (although the corresponding light chain CDRs are not present, collectively referred to in the art as variable heavy chain domains). . Alternatively, ABDs for TTAs can include three light chain CDRs (ie, CDR1, CDR2 and CDR3 of the VL region) and / or three heavy chain CDRs (ie, CDR1, CDR2 and CDR3 of the VH region). . The CD-3 binding domain preferably also includes at least the minimum structural requirements of the antibody allowing target binding. More preferably, the CD-3 binding domain comprises at least three light chain CDRs (ie, CDR1, CDR2 and CDR3 of the VL region) and / or three heavy chain CDRs (ie, CDR1, CDR2 and CDR3 of the VH region). Includes. In exemplary embodiments, the target antigen and / or CD-3 binding domain is contemplated as being produced by or obtainable by phage display or library screening methods.

As used herein, “domain” is meant to be a protein sequence having the function as outlined herein. Domains of the invention include tumor target antigen binding domains (TTA domains), variable heavy chain domains, variable light chain domains, linker domains, and half-life extending domains.

“Domain linker” as used herein is meant to be an amino acid sequence linking two domains, as outlined herein. The domain linker can be a cleavable linker, a constrained cleavable linker, a non-cleavable linker, a constrained non-cleavable linker, an scFv linker, and the like.

“Cleavable linker” (“CL”) herein is meant to be an amino acid sequence that can be cleaved by a protease, preferably a human protease, in diseased tissue, as outlined herein. Cleavable linkers are generally at least 3 amino acids in length, depending on the flexibility required, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more amino acids are seen. Find uses in the invention. A number of cleavable linker sequences are found in FIGS. 6 and 5.

As used herein, "non-cleavable linker" ("NCL") is meant to be an amino acid sequence that cannot be cleaved by a human protease under normal physiological conditions.

“Constrained cleavable linker” (“CCL”) herein is disclosed herein in such a way that the two domains cannot significantly interact with each other until after they reside on different polypeptide chains, eg, after cleavage. It is meant to be a short polypeptide containing a protease cleavage site (as defined herein) that connects these two domains. When CCL joins the VH and VL domains as defined herein, these VH and VL cannot self-assemble and form functional Fvs prior to cleavage due to steric constraints in the intramolecular manner (although they are in an intermolecular manner). Although it can be assembled into a pseudo Fv domain). Upon cleavage by the relevant protease, VH and VL can be assembled to form an active antigen binding domain in an intermolecular manner. In general, CCLs are no more than 10 amino acids in length, 9, 8, 7, 6, 5 and 4 amino acids find use in the present invention. Generally, the protease cleavage site is generally at least 4+ amino acids in length to confer sufficient specificity, as shown in FIG. 6.

“Constrained uncleavable linker” (“CNCL”) herein refers to these two domains in such a way that the two domains cannot significantly interact with each other and are not significantly cleaved by human proteases under physiological conditions. Is meant to be a short polypeptide linking as outlined herein.

As used herein, “constrained Fv domain” is disclosed herein in such a way that the active heavy chain and light chain variable domains interact in a molecule, making it impossible to form an active Fv that will bind an antigen, such as CD3. It is meant to be an Fv domain comprising an active variable heavy chain domain and an active variable light chain domain, covalently linked by a constrained linker. Thus, the restricted Fv domain is similar to scFv, but is unable to bind to the antigen due to the presence of a restricted linker (although they can assemble between inactive variable domains and molecules to form a pseudo Fv domain).

A “pseudo Fv domain” herein is a pseudo or inactive variable heavy chain domain or a pseudo or inactive variable light chain, linked using a domain linker (which can be cleavable, constrained, uncleasable, unconstrained, etc.) By domain, it is meant to be a domain comprising both. IVH and iVL domains of the pseudo Fv domain do not bind human antigens when associated with each other (iVH / iVL), or when associated with active VH or VL; Thus, the iVH / iVL, iVH / VL and iVL / VH Fv domains do not visibly bind human proteins to the extent that these domains become inactive in the human body.

“Single chain Fv” or “scFv” herein refers to a variable heavy chain (VH) covalently attached to a variable light chain (VL) domain, generally using a domain linker as discussed herein, to form an scFv or scFv domain. It is meant to be a domain. The scFv domain can be in either orientation (VH-linker-VL or VL-linker-VH) from N-terminus to C-terminus.

As used herein, “single domain Fv”, “sdFv” or “sdABD” is generally meant to be an antigen binding domain with only 3 CDRs based on camel antibody technology. Reference: Protein Engineering 9 (7): 1129-35 (1994); Rev Mol Biotech 74: 277-302 (2001); Ann Rev Biochem 82: 775-97 (2013). As outlined herein, two general types of sdABDs are used herein: sdABDs that bind to and thus comment on TTAs (sdABD-TTA in general terms, or sdABD-EGFR in the case of binding to EGFR). , SdABD-FOLR1, etc. in the case of binding to FOLR1), and sdABDs ("sdABD-HSA" or "sdABD (1/2)" binding to HSA.

"Protease cleavage site" refers to the amino acid sequence recognized and cleaved by a protease. Suitable protease cleavage sites are outlined below and are shown in FIGS. 5 and 6.

As used herein, “protease cleavage domain” means “protease cleavage site” and between individual protease cleavage sites and between protease cleavage site (s) and other functional components of the constructs of the invention (eg, V _H , V _L , iVH, iVL, target antigen binding domain (s), half-life extension domain, etc.). As outlined herein, protease cleavage domains can also include additional amino acids, if desired, for example, to impart flexibility.

The terms “COBRA ™” and “conditional bispecific forwarded activation” refer to bispecific conditionally effective proteins with multiple functional protein domains. In some embodiments, one of the functional domains is an antigen binding domain (ABD) that binds a target tumor antigen (TTA). In certain embodiments, other domains are ABDs that bind T cell antigens under certain conditions. T cell antigens include, but are not limited to, CD3. The term “hemi-COBRA ™” may be related to variable light chains of other hemi-COBRA ™ (complementary hemi-COBRA ™), due to innate self-assembly when concentrated on the surface of target expressing cells. When, refers to a conditionally effective protein capable of binding to a T cell antigen.

VII. Fusion protein of the invention

The fusion proteins of the invention have a number of different components collectively referred to herein as domains, which are linked together in various ways. Some of these domains are binding domains, each of which binds a target antigen (eg, TTA or CD3, for example). Because they bind one or more antigens, they are referred to herein as “multispecific”; For example, the prodrug constructs of the invention are capable of binding TTA and CD3, and are thus “bispecific”. Proteins can also have higher specificity; For example, if the first αTTA binds EGFR, the second binds EpCAM, and there is an anti-CD3 binding domain, it will be a “trispecific” molecule. Similarly, as shown in FIG. 3B, the addition of anti-HSA binding domains to these constructs will be “quasispecific”.

As will be appreciated by those skilled in the art, the proteins of the present invention not only have different binding costs, but can also be multispecific. In other words, the protein of the invention is capable of binding a target having one or more binding sites; For example, Pro140 is bivalent for EGFR.

Proteins of the invention can include CD3 antigen binding domains, tumor target antigen binding domains, half-life extension domains, linkers, etc., arranged in various ways as outlined herein.

A. CD3 antigen binding domain

The specificity of the T cell's response is mediated by recognition of the antigen (the major histocompatibility complex, presented in the context of MHC) by the T cell receptor complex. As part of the T cell receptor complex, CD3 is a protein complex comprising a CD3γ (gamma) chain, CD3δ (delta) chain, two CD3e (epsilon) chains and two CD3ζ (zeta) chains present on the cell surface. The CD3 molecule contains a TCR complex by interspersing with the α (alpha) and β (beta) chains of the T cell receptor (TCR). For example, clustering of CD3 on T cells by Fv domains that bind CD3 is similar to the inclusion of T cell receptors, but regardless of its clonal-typical specificity, causes T cell activation.

However, as is known in the art, CD3 activation can cause a number of toxic side effects, and thus the present invention relates to providing active CD3 binding of the polypeptides of the invention only in the presence of tumor cells in which a particular protease is found. However, the prodrug polypeptide of the present invention is then cleaved to provide an active CD3 binding domain. Thus, in the present invention, binding of the anti-CD-3 Fv domain to CD-3 is only in the microenvironment of diseased cells or tissues with elevated levels of protease, e.g., in the tumor microenvironment as described herein. It is regulated by a protease cleavage domain that limits the binding of the CD-3 Fv domain to CD-3.

Accordingly, the present invention provides two sets of VH and VL domains, an active set (VH and VL) and an inactive set (iVH and iVL), all of which are present in the prodrug construct. The construct is formatted such that the VH and VL sets are not self-correlated, but rather are compatible with inactive partners, eg, iVH and VL and iVL and VH as shown herein.

1. Active anti-CD3 variable heavy and variable light chain domains

There are a number of suitable active CDR sets and / or VH and VL domains known in the art that find use in the present invention. For example, CDRs and / or VH and VL domains are known anti-CD-3 antibodies, such as, for example, muromonab-CD-3 (OKT3), otelixizumab (TRX4), teplizumab (MGA031), Visilizumab (Nuvion), SP34 or I2C, TR-66 or X35-3, VIT3, BMA030 (BW264 / 56), CLB-T3 / 3, CRIS7, YTH12.5, F111-409, CLB- T3.4.2, TR-66, WT32, SPv-T3b, 11D8, XIII-141, XIII-46, XIII-87, 12F6, T3 / RW2-8C8, T3 / RW2-4B6, OKT3D, M-T301, SMC2, F101.01, derived from UCHT-1 and WT-31.

In one embodiment, the VH and VL sequences forming the active Fv domain that binds human CD3 are shown in FIG. 5. As shown herein, these active VH (“aVH”) and active VL (“aVL”) domains can be used in different shapes and types 1, 2, 3 and 4.

2. Inactive anti-CD3 variable heavy chain and variable light chain domains

Inactive iVH and iVL domains are such "regular" framework regions (FRs) that allow association, such that the inactive variable domain is compatible with the active variable domain such that the pair becomes inactive, e.g., unable to bind to CD3. It implies

As will be appreciated by those of skill in the art, there are a number of "inactive" variable domains found in use in the present invention. Basically, any variable domain with a human framework region that allows self-assembly with other variable domains can be used, even if some amino acids are in CDR positions within the variable region. For clarity, inactive domains are said to contain CDRs, although technically inactive variable domains do not confer binding capacity.

As is recognized in the art, producing an inactive VH or VL domain is generally simple and can be done in a variety of ways. In some embodiments, the calculation of an inactive variable domain is generally performed by altering one or more of the CDRs of an active Fv, including making changes in one or more of the three CDRs of the active variable domain. This can be done by making one or more amino acid substitutions at functionally important residues within one or more CDRs, replacing some or all CDR residues in random order, replacing one or more CDRs with a tag or flag sequence, and / or CDRs and / or variable regions can be acted by swapping unrelated antibodies (eg, from antibodies directed towards proteins of different organisms).

In some cases, although other embodiments include alterations in 1, 2, 3, 4, 5 or 6 CDRs, only one of the CDRs in the variable region can be altered to be inactive.

In some instances, inactive domains can be engineered to promote selective binding in the prodrug form to encourage the formation of intramolecular iVH-VL and VH-iVL domains prior to cleavage (eg, during intermolecular pairing). have. For example, Igawa et al., Protein Eng., Incorporated herein by reference in its entirety and specifically specifically for interface residue amino acid substitutions. Des. See Selection 23 (8): 667-677 (2010).

In certain embodiments, the CD-3 binding domain of the polypeptide constructs described herein exhibits strong CD-3 binding affinity with human CD-3 as well as excellent crossing with individual cynomolgus monkey CD-3 proteins. It shows reactivity. In some instances, the CD-3 binding domain of the polypeptide constructs of the invention is cross-reactive with CD-3 from cynomolgus monkeys. In certain instances, the human: cynomolgus KD ratio for CD-3 is between 5 and 0.2.

In some embodiments, the CD-3 binding domain of an antigen binding protein includes any domain that binds to CD-3, including but not limited to domains from monoclonal antibodies, polyclonal antibodies, recombinant antibodies, human antibodies, humanized antibodies. It can be a domain. In some cases, it is beneficial that the CD-3 binding domain is derived from the same species where the antigen binding protein will ultimately be used. For example, for use in humans, it may be beneficial for the CD-3 binding domain of the antigen binding protein to include human or humanized residues from the antigen binding domain of the antibody or antibody fragment.

Thus, in one aspect, the antigen binding domain comprises a humanized or human binding domain. In one embodiment, the humanized or human anti-CD-3 binding domain is a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2) of the humanized or human anti-CD-3 binding domain described herein. And one or more (e.g., all three) of the light chain complementarity determining regions 3 (LC CDR3) and / or heavy chain complementarity determining regions 1 (HC CDR1) of the humanized or human anti-CD-3 binding domains described herein. ), One or more of heavy chain complementarity determining regions 2 (HC CDR2) and heavy chain complementarity determining regions 3 (HC CDR3) (e.g., all three), e.g. humanized or human anti-CD- The three binding domains include one or more of the LC CDRs, eg, all three and one or more of the HC CDRs, eg, all three.

In some embodiments, the humanized or human anti-CD-3 binding domain comprises a humanized or human light chain variable region specific for CD-3, wherein the light chain variable region specific for CD-3 is a human light chain framework region Within human or non-human light chain CDRs. In certain instances, the light chain framework region is a λ (lambda) light chain framework. In another example, the light chain framework region is a κ (kappa) light chain framework.

In some embodiments, one or more CD-3 binding domains are humanized or fully human. In some embodiments, one or more activated CD-3 binding domains have a KD binding of 1000 nM or less to CD-3 on CD-3 expressing cells. In some embodiments, one or more activated CD-3 binding domains have a KD binding of 100 nM or less to CD-3 on CD-3 expressing cells. In some embodiments, one or more activated CD-3 binding domains have a KD binding of 10 nM or less to CD-3 on CD-3 expressing cells. In some embodiments, one or more CD-3 binding domains are cross-reactive with cynomolgus CD-3. In some embodiments, one or more of the CD-3 binding domains comprises an amino acid sequence provided herein.

In some embodiments, the humanized or human anti-CD-3 binding domain comprises a humanized or human heavy chain variable region specific for CD-3, wherein the heavy chain variable region specific for CD-3 is a human heavy chain framework region Within human or non-human heavy chain CDRs.

In one embodiment, the anti-CD-3 binding domain is Fv comprising the light and heavy chains of the amino acid sequence provided herein. In one embodiment, the anti-CD-3 binding domain comprises: at least one, two, or three modifications (eg, substitutions) of the amino acid sequence of the light chain variable region provided herein, but 30, A light chain variable region comprising an amino acid sequence having no more than 20 or 10 modifications (eg, substitutions), or a sequence having 95-99% identity to the amino acid sequence provided herein; And / or at least one, two, or three modifications (eg, substitutions) of the amino acid sequence of the heavy chain variable region provided herein, but no more than 30, 20, or 10 modifications (eg, substitutions) ), Or a heavy chain variable region comprising a sequence having 95-99% identity to the amino acid sequence provided herein. In one embodiment, the humanized or human anti-CD-3 binding domain is scFv, and the light chain variable region comprising the amino acid sequence described herein is via a scFv linker, a heavy chain variable region comprising the amino acid sequence described herein. It is attached to. The light chain variable region and heavy chain variable region of the scFv can be at any orientation, for example: light chain variable region-scFv linker-heavy chain variable region or heavy chain variable region-scFv linker-light chain variable region.

In some embodiments, the CD-3 binding domain of an antigen binding protein is 1000 nM or less, 100 nM or less, 50 nM or less, 20 nM or less, 10 nM or less, 5 nM or less , Has an affinity for CD-3 on CD-3 expressing cells with a KD of 1 nM or less, or 0.5 nM or less. In some embodiments, the CD-3 binding domain of an antigen binding protein is 1000 nM or less, 100 nM or less, 50 nM or less, 20 nM or less, 10 nM or less, 5 nM or less , 1 nM or less, or 0.5 nM or less with a KD of affinity for CD-3ε. In a further embodiment, the CD-3 binding domain of the antigen binding protein has a low affinity for CD-3, i.e., about 100 nM or higher.

Affinity to CD-3 binding is coated on an assay plate, typically using a Biacore or Octet assay, for example, as known in the art; Exhibited on the surface of microbial cells; In a dissolved state; And the like, or by the ability of the antigen-binding protein itself to bind CD-3 or its CD-3 binding domain. The binding activity of the antigen binding protein of the present invention or its CD-3 binding domain to CD-3 beads a ligand (e.g., CD-3) or antigen binding protein itself or its CD-3 binding domain, It can be assayed by immobilization on a substrate, cell, etc. The agent can be added in a moderate buffer, and the binding partner can be incubated for a period of time at a given temperature. After washing to remove unbound material, the bound protein is released into, for example, SDS, a buffer with high pH, etc., and can be analyzed, for example, by surface plasmon resonance (SPR).

In many embodiments, preferred active and inactive binding domains are those depicted in FIG. 5.

B. Antigen binding domain to tumor target antigen

In addition to the described CD3 and half-life extending domains, the polypeptide constructs described herein also include one or more target antigens, or target domains that bind one or more regions on a single target antigen. Herein, the polypeptide constructs of the invention are cleaved in a protease cleavage domain, eg, in a disease specific microenvironment or in the blood of an individual, and each target antigen binding domain binds a target antigen on a target cell, and thus T It is expected to activate the CD3 binding domain that binds cells. In general, TTA binding domains are able to bind their targets prior to protease cleavage, so they can “standby” on target cells and then become activated as T-cell engagers. At least one target antigen is associated with and / or associated with a disease, disorder or condition. Exemplary target antigens include proliferative diseases, tumor diseases, inflammatory diseases, immunological disorders, autoimmune diseases, infectious diseases, viral diseases, allergic reactions, parasitic reactions, graft-to-host disease or those associated with host-to-graft disease. In some embodiments, the target antigen is a tumor antigen expressed in tumor cells. Alternatively, in some embodiments, the target antigen is associated with a pathogen, such as a virus or bacteria. The at least one target antigen may also be directed towards healthy tissue.

In some embodiments, the target antigen is a cell surface molecule, such as a protein, lipid or polysaccharide. In some embodiments, the target antigen is on tumor cells, virus infected cells, bacterial infected cells, damaged red blood cells, arterial plaque cells, or fibrotic tissue cells.

A preferred embodiment of the invention utilizes sdABDs as targeting domains. These are preferred over scFv ABDs because the addition of other VH and VL domains into the constructs of the present invention can complicate the formation of pseudo Fv domains.

In some embodiments, prodrug constructs of the invention utilize a single TTA binding domain, such as the one depicted generally in FIG. 3A as a pair of sdABD-TTAs, and the one depicted generally in FIG. 4 as a “form 4” shape. do. 4 depicts the use of a single anti-EGFR ABD, although other TTA binding domains may be used.

In some embodiments, particularly in Form 1 and Form 2 constructs, the prodrug constructs of the invention once again utilize two TTA ABDs, preferably in the sdABD-TTA form. When dual targeting domains are used, they can bind the same epitope of the same TTA. For example, as discussed herein, most of the constructs herein utilize two identical targeting domains. In some embodiments, two targeting domains can be used that bind different epitopes of the same TTA, for example, as shown in FIG. 5, these two EGFR sdABDs bind different epitopes on human EGFR. In some embodiments, two targeting domains bind different TTAs (see, eg, FIG. 54).

Polypeptide constructs contemplated herein include at least one antigen binding domain, wherein the antigen binding domain binds at least one target antigen. In some embodiments, the target antigen binding domain specifically binds cell surface molecules. In some embodiments, a target antigen binding domain specifically binds a tumor antigen. In some embodiments, the target antigen binding domain is specifically for a tumor target antigen (“TTA”) selected from at least one of EpCAM, EGFR, HER-2, HER-3, cMet, LyPD3, B7H3, CEA and FOLR1. And independently.

In particular, sdABDs for human EGFR, as shown in Figure 5, are used in the present invention.

In a further embodiment, sdABDs for human FOLR1, as shown in FIG. 5, are used in the present invention.

In a further embodiment, sdABDs for human B7H3, as shown in FIG. 5, are used in the present invention.

In further embodiments, sdABDs for human EpCAM, as shown in FIG. 5, are used in the present invention.

In some embodiments, the protein before cleavage of the protease cleavage domain is less than about 100 kDa. In some embodiments, the protein after cleavage of the protease cleavage domain is about 25 to about 75 kDa. In some embodiments, the protein before protease cleavage has a size that exceeds the kidney threshold for first pass loss. In some embodiments, the protein before cleavage of the protease has an elimination half-life of at least about 50 hours. In some embodiments, the protein before cleavage of the protease has an elimination half-life of at least about 100 hours. In some embodiments, the protein has increased tissue penetration to the same target antigen compared to IgG. In some embodiments, the protein has increased tissue distribution to the same target antigen compared to IgG.

C. Half-life extension domain

The MCE protein of the invention (again, also referred to herein as a “COBRA ™” protein or construct) optionally comprises a half-life extending domain. It is contemplated that such domains include, but are not limited to, HSA binding domains, Fc domains, small molecules, and other half-life extension domains known in the art.

Human serum albumin (HSA) (molecular mass ~ 67 kDa) is the most abundant protein present at about 50 mg / ml (600 uM) in plasma, and has a half-life of about 20 days in humans. HSA plays a role in maintaining plasma pH, contributes to colloidal blood pressure, functions as a carrier for many metabolites and fatty acids, and serves as a major drug transport protein in plasma.

The non-covalent association with albumin extends the elimination half-life of short-lived proteins. For example, recombinant fusion of albumin binding domains to Fab fragments resulted in 25-fold and 58-fold reduced in vivo loss and 26-fold, respectively, when administered intravenously to mice and rabbits, compared to administration of Fab fragment alone. The half-life extension of the pear and 37-fold was induced. In another example, a delayed effect was observed when insulin was acylated with fatty acids to promote association with albumin, when injected subcutaneously in rabbits or pigs. Taken together, these studies demonstrate a link between albumin binding and prolonged action.

In one aspect, the antigen binding protein described herein comprises a half-life extending domain, such as a domain that specifically binds HSA. In other embodiments, the HSA binding domain is a peptide. In a further embodiment, the HSA binding domain is a small molecule. The HSA binding domain of the antigen binding protein is fairly small, and in some embodiments is expected to be within 25 kD, within 20 kD, within 15 kD, or within 10 kD. In certain instances, the HSA binding domain is 5 kD or less if it is a peptide or small molecule.

In many embodiments, the half-life extending domain is a single domain antigen binding domain from a single domain antibody that binds HSA. These domains are collectively referred to herein as “sdABD” (sdABD-HSA) for human HSA, or alternatively “sdABD (1/2)” to identify these binding domains from sdABDs for TTAs. A particularly useful sdABD (1/2) is shown in FIG. 5.

The half-life extending domain of the antigen-binding protein provides the altered pharmacodynamics and pharmacokinetics of the antigen-binding protein itself. As above, the half-life extending domain extends the elimination half-life. The half-life extending domain also alters pharmacokinetic properties, including alteration of tissue distribution, penetration and spread of antigen binding proteins. In some embodiments, the half-life extending domain provides enhanced tissue (including tumor) targeting, tissue penetration, tissue distribution, diffusion in tissue, and enhanced potency, as compared to proteins without a half-life extending binding domain. In one embodiment, the method of treatment effectively and efficiently utilizes a reduced amount of antigen binding protein, leading to reduced side effects, such as reduced non-tumor cell cytotoxicity.

In addition, features of the half-life extending domain, eg, HSA binding domain, include the binding affinity of the HSA binding domain to HSA. The affinity of the HSA binding domain can be selected to target a specific elimination half-life in a particular polypeptide construct. Thus, in some embodiments, the HSA binding domain has a high binding affinity. In other embodiments, the HSA binding domain has an intermediate binding affinity. In another embodiment, the HSA binding domain has a low or minimal binding affinity. Exemplary binding affinity includes concentrations of KD of 10 nM or less (high), between 10 nM and 100 nM (medium), and greater than (lower) 100 nM. As above, the binding affinity for HSA is determined by known methods, such as surface plasmon resonance (SPR).

D. Protease cleavage site

Protein compositions of the invention, and in particular prodrug constructs, as outlined herein, include one or more protease cleavage sites generally residing within a cleavable linker.

As described herein, a prodrug construct of the invention comprises at least one protease cleavage site comprising an amino acid sequence cleaved by at least one protease. In some cases, the MCE protein described herein is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 cleaved by at least one protease , 17, 18, 19, 20, or more protease cleavage sites. As discussed more fully herein, when one or more protease cleavage sites are used in prodrug construction, they can be the same (eg, multiple sites cleaved by a single protease) or different (two or more thereof). These cleavage sites are cleaved by at least two different proteases). As recognized by those of skill in the art, constructs containing three or more protease cleavage sites can utilize one, two, three, etc .; For example, some constructs can utilize three sites for two different proteases, etc.

The amino acid sequence of the protease cleavage site will depend on the protease being targeted. As is known in the art, there are a number of human proteases found in the body and can be associated with disease states.

It is known that proteases are secreted by some diseased cells and tissues, such as tumor or cancer cells, to create a protease-rich microenvironment or a protease-rich microenvironment. In some cases, the subject's blood is protease-rich. In some cases, the cells surrounding the tumor secrete proteases into the tumor microenvironment. The cells surrounding the tumor that secrete proteases are tumor interstitial cells, myofibroblasts, blood cells, mast cells, B cells, NK cells, regulatory T cells, macrophages, cytotoxic T lymphocytes, dendritic cells, mesenchymal stem cells, polymorphism Nuclear cells, and other cells. In some instances, proteases, such as proteases targeting amino acid sequences found in microbial peptides, are present in the subject's blood. These traits allow targeted therapeutics, such as antigen binding proteins, to have additional specificity, because T cells will not be bound by these antigen binding proteins, except in the protease-rich microenvironment of targeted cells or tissues. to be.

Proteases, in some cases, are proteins that cleave proteins in a sequence-specific manner. Proteases include serine protease, cysteine protease, aspartate protease, threonine protease, glutamic acid protease, metalloproteinase, asparagine peptide lyase, serum protease, cathepsin (e.g. cathepsin B, cathepsin C, cathepsin D, cathesin Tepsin E, cathepsin K, cathepsin L, cathepsin S), kallikrein, hK1, hK10, hK15, KLK7, granzyme B, plasmin, collagenase, type IV collagenase, stromelysin, factor XA , Chymotrypsin-like protease, trypsin-like protease, elastase-like protease, subtilisin-like protease, actinidine, bromelain, calpein, caspase (e.g. caspase-3), Mir1-CP, papain, HIV-1 protease, HSV protease, CMV protease, chymosin, lenin, pepsin, matriptase, legumine, plasticin, nepenthesin, metalloexopeptidase, metalloene Dopeptidase, Substrate Metal Protease (MMP), MMP1, MMP2, MMP3, MMP8, MMP9, MMP13, MMP11, MMP14, Mephrin, Urokinase Plasminogen Activator (uPA), Enterokinase, Prostate-specific Antigen (PSA, hK3), interleukin-1β converting enzyme, thrombin, FAP (FAP-α), dipeptidyl peptidase, and dipeptidyl peptidase IV (DPPIV / CD26).

Some suitable proteases and protease cleavage sequences are shown in FIGS. 5 and 6.

E. Linker

As discussed herein, different domains of the invention are generally amino acid linkers that can also confer functionality, including flexibility or inefficiency (eg, steric pharmaceuticals), as well as the ability to cleave using native proteases. Are connected together. These linkers can be classified in a variety of ways.

The present invention provides “domain linkers”, which are two or more domains (eg, VH and VL, target tumor antigen binding domains (TTABD, sometimes referred to herein as “αTTA” ”(for“ anti-TTA ”)) Also referred to as VH or VL, half-life extending domains to other components, and the like, etc. Domain linkers are, for example, non-cleavable (NCL), cleavable (“CL”). , Constrained cleavable (CCL), and constrained non-cleavable (CNCL),

1. Non-cleavable linker

In some embodiments, domain linkers are non-cleavable. In general, they can be one of two types: non-cleavable and flexible types that allow the "upstream" and "downstream" components of the linker in the construct to self-assemble in the molecule in a certain way; Or a non-cleavable and constrained type in which these two components separated by the linker cannot be self-assembled intramolecularly. However, it should be noted that in the latter case, the two component domains separated by the non-cleavable constrained linker are not self-assembled intramolecularly, but the other intramolecular components self-assemble to form a pseudo Fv domain.

(i) Non-cleavable but flexible linker

In this embodiment, the linker is generally used to link these domains to preserve the functionality of the domain, through longer and more flexible domains that are not cleaved by the original protease in the patient. Examples of internal, non-cleavable linkers suitable for joining domains in the polypeptides of the invention include (GS) n, (GGS) n, (GGGS) n, (GGSG) n, (GGSGG) n, or (GGGGS) n Includes, but is not limited to, where n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments the linker may be about 15 amino acids in length.

(ii) non-cleavable and constrained linker

In some instances, the linker does not contain cleavage sites, and is also too short to allow the intramolecular self-assembly of the protein domains separated by these linkers, and “constrained non-cleatable linkers” or “CNCLs” to be. For example, in Pro186, active VH and active VL are separated by 8 amino acids (“8mers”) that do not allow these VHs and VLs to self-assemble into active antigen binding domains. In some embodiments, the linker is still flexible; For example, (GGGS) n where n = 2. In other embodiments, although less generally preferred, more rigid linkers, such as proline or those containing bulky amino acids, can be used.

2. Cleavable linker

All prodrug constructs herein include at least one cleavable linker. Thus, in one embodiment, the domain linker is cleavable (CL), sometimes referred to herein as a “protease cleavage domain” (“PCD”). In this embodiment, CL contains a protease cleavage site, as outlined herein and depicted in FIGS. 5 and 6. In some cases, CL contains only the protease cleavage site. Optionally, depending on the length of the cleavage recognition site, there may be additional few connecting amino acids at either or both the N- or C-terminal end of CL; For example, there may be 1, 2, 3, 4 or 5 amino acids on either or both of the N and C ends of the cleavage site. Thus, a cleavable linker can also be constrained (eg 8mers) or flexible.

MMP9 cleavable linkers and mephrine cleavable linkers, in particular MMP9 constrained cleavable linkers and mephrine constrained cleavable linkers, are of particular interest in the present invention.

VIII. Domain of the present invention

The present invention provides a number of different formats for the prodrug polypeptides of the invention. The present invention provides constrained Fv domains and constrained pseudo Fv domains. Additionally, the present invention provides multivalent conditionally effective ("MCE") proteins, which contain two Fv domains but are non-isomerized constructs. As outlined herein, although all constructs contain at least one protease cleavage domain, they can be in a non-isomerizable cleavable form or a non-isomerizable non-cleavable form.

Importantly, both of these domains (Fv domain and pseudo Fv domain) are referred to herein as “constrained”, which are discussed and discussed above, although proteins generally have better expression when both linkers are constrained. 36, 37 and 38, it means that only one of them needs to be restricted.

Those skilled in the art will recognize that in the case of types 1, 2 and 4, there are four possibilities for the N-to-C-terminal sequence of the restricted caustic Fv domain of the present invention (linkers not shown): aVH-aVL and iVL-iVH, aVH-aVL and iVH-iVL, aVL-aVH and iVL-iVH, aVL-aVH and iVH-iVL. All four were tested, and although the first order, aVH-aVL and iVL-iVH showed better expression than the other three, all four are active. Thus, although the description herein is generally shown in these aVH-aVL and iVL-iVH formats, all disclosures herein also include other sequences for these domains.

Note that, in general, the N-to-C-terminal sequence for the full-length constructs of the present invention is based on aVH-aVL and iVL-iVH orientation.

Additionally, it is known in the art that there may be immunogenicity originating from the C-terminal sequence of certain ABDs in humans. Thus, in general, histidine tags (either His6 or His10) can be used, particularly when the C-terminus of the construct is terminated in sdABD (eg, most sdABD-HSA domains in the construct). Although many or most of the sequences were generated using His6 C terminal tags for purification reasons, these sequences were also human, as shown by Holland et al., DOI 10.1007 / s10875-013-9915-0 and WO2013 / 024059 Can be used to reduce immunogenicity.

A. Constrained Fv domain

The invention provides active VH and active VL domains that are covalently attached using a constrained linker (which can be cleavable (forms 1 and 3) or non-cleavable (forms 2 and 4), as outlined herein). Containing Fv domains are provided. The constrained linker prevents an intramolecular association between aVH and aVL in the absence of cleavage. Thus, the restricted Fv domain generally comprises a set of 6 CDRs nested within the variable domain, where vhCDR1, vhCDR2 and vhCDR3 of VH bind to human CD-3 and vlCDR1, vCDR2 and vlCDR3 of VL are human CD Binds to -3, but in prodrug form (e.g., not cleaved) these VHs and VLs cannot sterically associate to form active binding domains, but instead prefer to intramolecularly associate with caustic Fv. do.

Constrained Fv domains can include active VH and active VL (aVH and aVL) or inactive VH and VL (iVH and iVL, if this is a restricted pseudo Fv domain) or combinations thereof, as described herein. .

As will be appreciated by those skilled in the art, the order of VH and VL in the restricted Fv domain can be either VH-linker-VL or VL-linker-VH (from N-terminus to C-terminus).

As outlined herein, in the case of Form 1 constructs, the restricted Fv domain can include VH and VL linked using a cleavable linker in cases such as those shown in FIGS. 5 and 6. In this embodiment, the restricted Fv domain has the following structure (from N-terminus to C-terminus): vhFR1-vhCDR1-vhFR2-vhCDR2-vhFR3-vhCDR3-vhFR4-CCL-vlFR1-vlCDR1-vlFR2-vlCDR2-vlFR3-vlCDR3-vlFR4 Have In general, the restricted Fv domain contains the active VH and VL domains (e.g., capable of binding to CD3 when involved), and thus the following structure (from N-terminus to C-terminus): vhFR1-avhCDR1- vhFR2-avhCDR2-vhFR3-avhCDR3-vhFR4-CCL-vlFR1-avlCDR1-vlFR2-avlCDR2-vlFR3-avlCDR3-vlFR4.

As outlined herein, in the case of Form 2 constructs, the restricted Fv domain may include VH and VL linked using a non-cleavable linker. In this embodiment, the restricted Fv domain has the following structure (from N-terminus to C-terminus): vhFR1-vhCDR1-vhFR2-vhCDR2-vhFR3-vhCDR3-vhFR4-CNCL-vlFR1-vlCDR1-vlFR2-vlCDR2-vlFR3-vlCDR3-vlFR4 Have In general, the restricted Fv domain contains the active VH and VL domains (e.g., capable of binding to CD3 when involved), and thus the following structure (from N-terminus to C-terminus): vhFR1-avhCDR1- vhFR2-avhCDR2-vhFR3-avhCDR3-vhFR4-CNCL-vlFR1-avlCDR1-vlFR2-avlCDR2-vlFR3-avlCDR3-vlFR4.

In particular, constrained uncleavable Fv domains having aVH with SEQ ID NO: 61, aVL with SEQ ID NO: 49, and a domain linker with SEQ ID NO: 74 are used in the present invention.

B. Constrained Caustic Fv Domain

The present invention provides constrained pseudo Fv domains comprising inactive or pseudo iVH and iVL domains that are covalently attached using a constrained linker (which can be cleavable or non-cleavable, as outlined herein). The constrained linker prevents an intramolecular association between iVH and iVL in the absence of cleavage. Thus, although the resulting pseudo Fv domain does not bind to human proteins, the constrained pseudo Fv domain generally provides iVH and iVL with a framework region that allows the association of iVH and iVL (in unconstrained form). Includes. Although the resulting structure does not bind to CD3, the iVH domain can be assembled with the aVL domain, and the iVL domain can be assembled with the aVH domain.

Constrained pseudo Fv domains include inactive VH and VL (iVH and iVL).

As will be appreciated by those skilled in the art, the order of VH and VL in the restricted pseudo Fv domain can be either VH-linker-VL or VL-linker-VH (from N-terminus to C-terminus).

As outlined herein, constrained pseudo Fv domains are iVH linked using a cleavable linker, as shown in Forms 1, 2 and 4, or as shown in Form 3, using a cleavable linker. And iVL.

In general, the restricted Fv domain contains inactive VH and VL domains (e.g., capable of binding to CD3 when associated), and, thus, the following structure (from N-terminus to C-terminus): vhFR1-ivlCDR1- vhFR2-ivlCDR2-vhFR3-ivlCDR3-vhFR4-CNCL-vlFR1-ivhCDR1-vlFR2-ivhCDR2-vlFR3-ivhCDR3-vlFR4.

In particular, the present invention is a constrained non-cleavable pseudo Fv domain having iVH having SEQ ID NO: 65 or SEQ ID NO: 69, iVL having SEQ ID NO: 53 or SEQ ID NO: 57, and a domain linker having SEQ ID NO: 74. It is used in.

IX. Form of the invention

As discussed herein, the prodrug constructs of the invention have a cleavable form with a dual TTA binding domain, a dual TTA binding domain, either of which may have the same TTA binding domain or a different binding domain. A number of different formats can be taken, including non-cleavable formats, and non-cleavable formats with a single targeting domain.

A. Cleavable format with dual targeting

The present invention provides a non-isomerizable cleavable format of type “Type 1” in FIG. 1. In this embodiment, the constrained Fv domain comprises VH and VL domains linked using a constrained cleavable linker, and the constrained pseudo Fv domains use constrained non-cleavable linkers. For ease of discussion, both of which are referred to herein as “restricted”, but as discussed above and shown in FIGS. 36, 37 and 38, although generally, when both linkers are constrained, the protein becomes more Although it has good expression, only one of them needs to be restricted.

All constructs in format 1 (as well as other formats) also have a cleavable linker (CL) that is cleaved by a human tumor protease.

The present invention comprises (sdABD-TTA1) -domain linker-restricted Fv domain-domain linker- (sdABD-TTA2) -CL-restricted pseudo Fv domain-domain linker-sdABD-HSA from N-terminus to C-terminus. Prodrug proteins are provided.

As will be appreciated by those skilled in the art, the order of VH and VL in either the constrained Fv domain or the constrained pseudo Fv domain is either VH-linker-VL or VL-linker-VH (from N-terminus to C-terminus). Can be

Thus, in one embodiment, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL -CNCL-iVH-domain linker-sdABD-HSA.

Thus, in one embodiment, the prodrug protein comprises, from N-terminus to C-terminus: (sdABD-TTA1) -domain linker-aVH-CCL-aVL-domain linker- (sdABD-TTA2) -CL-iVH -CCL-iVL-domain linker-sdABD-HSA.

Thus, in one embodiment, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVL-CCL-aVH-domain linker- (sdABD-TTA2) -CL-iVL -CCL-iVH-domain linker-sdABD-HSA.

Thus, in one embodiment, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVL-CCL-aVH-domain linker- (sdABD-TTA2) -CL-iVH -CCL-iVL-domain linker-sdABD-HSA.

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-NCL-sdABD (1/2) do. In this embodiment, aVH, aVL, iVH and iVL have the sequence shown in FIG. 5.

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-domain linker-sdABD (1/2). Includes. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind the same TTA, which can be EGFR, EpCAM, FOLR1 or B7H3 (the sequence for these is depicted in Figure 5).

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-domain linker-sdABD (1/2). Includes. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind different TTAs.

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-domain linker-sdABD (1/2). Includes. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind EGFR and EpCAM, and sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-domain linker-sdABD (1/2). Includes. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, two targeting domains bind EGFR and FOLR1, and sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-domain linker-sdABD (1/2). Includes. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, two targeting domains bind EGFR and B7H3, and sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-domain linker-sdABD (1/2). Includes. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind EpCAM and FOLR1, and the sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-domain linker-sdABD (1/2). Includes. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, two targeting domains bind EpCAM and B7H3, and sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-domain linker-sdABD (1/2). Includes. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind B7H3 and FOLR1, and the sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, a prodrug construct comprises sdABD (TTA1) -domain linker-aVH-CCL-aVL-domain linker-sdABD (TTA2) -CL-iVL-CNCL-iVH-domain linker-sdABD (1/2). Includes. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind to the same TTA, which can be EGFR, FOLR1, B7H3 or EpCAM (sequences for these are depicted in Figure 5), and CCL and CL cleaved by MMP9 or mephrine Selected from the linker, and sdABD (1/2) has SEQ ID NO: 45.

In format 1, the preferred domain linker is SEQ ID NO: 74 (this also serves as a preferred restricted non-cleavable linker).

In Form 1, preferred constructs are Pro140 and Pro140b.

B. Non-cleatable form

As shown in Figure 2, the present invention provides a non-isomerizable non-cleavable form. In this embodiment, “non-cleatable” is understood to apply only to the chain of restricted Fv domains, because there is an active cleavage site within the prodrug construct. In this embodiment, the constrained Fv domain comprises VH and VL domains linked using a constrained non-cleavable linker, and the constrained pseudo Fv domain uses a constrained non-cleavable linker.

As will be appreciated by those skilled in the art, the order of VH and VL in either the constrained Fv domain or the constrained pseudo Fv domain is either VH-linker-VL or VL-linker-VH (from N-terminus to C-terminus). Can be

The invention comprises an sdABD (TTA1) -domain linker-restricted Fv domain-domain linker-sdABD (TTA2) -cleavable linker-restricted caustic Fv domain-domain linker-sdABD-HSA from N-terminus to C-terminus Prodrug proteins are provided.

As will be appreciated by those skilled in the art, the order of VH and VL in either the constrained Fv domain or the constrained pseudo Fv domain is either VH-linker-VL or VL-linker-VH (from N-terminus to C-terminus). Can be

Thus, in one embodiment, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL -CNCL-iVH-domain linker-sdABD-HSA.

Thus, in one embodiment, the prodrug protein comprises, from N-terminus to C-terminus: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVH -CNCL-iVL-domain linker-sdABD-HSA.

Thus, in one embodiment, the prodrug protein includes, from N-terminus to C-terminus: (sdABD-TTA1) -domain linker-aVL-CNCL-aVH-domain linker- (sdABD-TTA2) -CL-iVL -CNCL-iVH-domain linker-sdABD-HSA.

Thus, in one embodiment, the prodrug protein includes, from N-terminus to C-terminus: (sdABD-TTA1) -domain linker-aVL-CNCL-aVH-domain linker- (sdABD-TTA2) -CL-iVH -CNCL-iVL-domain linker-sdABD-HSA.

In some embodiments, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL-CNCL -iVH-domain linker-sdABD-HSA. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind the same TTA, which can be EGFR, EpCAM, FOLR1 or B7H3 (the sequence for these is depicted in Figure 5).

In some embodiments, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL-CNCL -iVH-domain linker-sdABD-HSA. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind different TTAs.

In some embodiments, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL-CNCL -iVH-domain linker-sdABD-HSA. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind EGFR and EpCAM, and sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL-CNCL -iVH-domain linker-sdABD-HSA. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, two targeting domains bind EGFR and FOLR1, and sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL-CNCL -iVH-domain linker-sdABD-HSA. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, two targeting domains bind EGFR and B7H3, and sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL-CNCL -iVH-domain linker-sdABD-HSA. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind EpCAM and FOLR1, and the sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL-CNCL -iVH-domain linker-sdABD-HSA. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, two targeting domains bind EpCAM and B7H3, and sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL-CNCL -iVH-domain linker-sdABD-HSA. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind FOLR1 and B7H3, and the sdABD-TTAs have the sequence in FIG. 5.

In some embodiments, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA1) -domain linker-aVH-CNCL-aVL-domain linker- (sdABD-TTA2) -CL-iVL-CNCL -iVH-domain linker-sdABD-HSA. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the two targeting domains bind to the same TTA, which can be EGFR, FOLR1, B7H3 or EpCAM (sequences for these are depicted in Figure 5), and CCL and CL cleaved by MMP9 or mephrine Selected from the linker, and sdABD (1/2) has SEQ ID NO: 45.

In format 2, the preferred domain linker is SEQ ID NO: 74 (this also serves as a preferred restricted non-cleavable linker).

In format 2, specific use specific examples include Pro186, Pro225, Pro226, Pro233, Pro311, Pro312, Pro313, Pro495, Pro246, Pro254, Pro255, Pro256, Pro420, Pro421, Pro432, Pro479, Pro480, Pro187, Pro221, Pro222, Pro223, Pro224, Pro393, Pro394, Pro395, Pro396, Pro429, Pro430 and Pro431.

C. Single TTA construct

As shown in FIG. 4, a “Form 4” construct similar to Form 2 construct but without a second TTA ABD is also included within the compositions of the present invention. In this embodiment, “non-cleatable” is understood to apply only to the chain of restricted Fv domains, because there is an active cleavage site within the prodrug construct. In this embodiment, the constrained Fv domain comprises VH and VL domains linked using a constrained non-cleavable linker, and the constrained pseudo Fv domain uses a constrained non-cleavable linker.

As will be appreciated by those skilled in the art, the order of VH and VL in either the constrained Fv domain or the constrained pseudo Fv domain is either VH-linker-VL or VL-linker-VH (from N-terminus to C-terminus). Can be

The present invention provides a prodrug protein comprising an sdABD (TTA) -domain linker-restricted Fv domain-cleavable linker-sdABD-HSA-restricted pseudo Fv domain from N-terminus to C-terminus. (Note that for all constructs of this type, sdABD-HSA generally does not have this, although His6 tags may be included).

As will be appreciated by those skilled in the art, the order of VH and VL in either the constrained Fv domain or the constrained pseudo Fv domain is either VH-linker-VL or VL-linker-VH (from N-terminus to C-terminus). Can be

Thus, in one embodiment, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA) -domain linker-aVH-CNCL-aVL-CL- (sdABD-HSA) -domain linker-iVL -CNCL-iVH.

Thus, in one embodiment, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA) -domain linker-aVH-CNCL-aVL-CL- (sdABD-HSA) -domain linker-iVH -CNCL-iVL.

Thus, in one embodiment, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA) -domain linker-aVL-CNCL-aVH-CL- (sdABD-HSA) -domain linker-iVH -CNCL-iVL.

Thus, in one embodiment, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA) -domain linker-aVL-CNCL-aVH-CL- (sdABD-HSA) -domain linker-iVL -CNCL-iVH.

Thus, in one embodiment, the prodrug protein is from N-terminus to C-terminus, including: (sdABD-TTA) -domain linker-aVH-CNCL-aVL-CL- (sdABD-HSA) -domain linker-iVL -CNCL-iVH. In this embodiment, aVH, aVL, iVH, iVL have the sequence shown in FIG. 5. In this embodiment, the targeting domain binds TTA, which can be EGFR, EpCAM, FOLR1 or B7H3 (the sequence for which is depicted in Figure 5).

In format 4, the preferred domain linker is SEQ ID NO: 74 (this also serves as a preferred restricted non-cleavable linker).

In format 4, the preferred sdABD-HSA is of SEQ ID NO: 45.

D. Two protein compositions

In some embodiments, compositions of the invention comprise two different molecules, sometimes referred to as “hemi-COBRAs ™”, or “hemi-constructs”, which in the absence of cleavage associate intramolecularly to form pseudo-Fvs. do. In the presence of the protease, as depicted overall in Figure 3, the cleavage site cleaves to release the inactive variable domain, and then the protein pair forms an active antigen binding domain for CD3.

An important point in the design of hemi-constructs is that the active variable domain and sdABD-TTA remain together after cleavage, so that these two cleaved portions are bound by tumor antigen receptors on the tumor surface, and thereafter, active anti-CD3 binding. It is possible to form a domain.

There are two different general format 3 constructs: those with each member of the pair having a single sdABD-TTA (FIG. 3A), and each having two different sdABD-TTAs for different TTAs (FIG. 3B).

1. Hemi-COBRA ™ construct with a single TTA binding domain (Form 3A)

In some embodiments, the first hemi-COBRA ™ has an sdABD (TTA1) -domain linker-aVH-CL-iVL-domain linker- sdABD (1/2) from the N-terminus to the C-terminus, and the second one is sdABD (1/2) -domain linker-iVH-CL-aVL-domain linker-sdABD (TTA2). In this embodiment, aVH, aVL, iVH, iVL and sdABD (1/2) have the sequence shown in Figure 5, and sdABD-TTAa binds human EGFR, EpCAM, FOLR1 and / or B7H3 and in Figure 5 It has the sequence depicted.

2. Hemi-COBRA ™ constructs with dual TTA ABDs

In some embodiments, a conjugated prodrug construct can have two sdABD-TTA binding domains per construct, as shown in FIG. 3B. In this embodiment, the first member of the pair comprises an sdABD-TTA1-domain linker-sdABD-TTA2-domain linker-aVH-CL-iVL-domain linker-sdABD (HAS) from N-terminus to C-terminus, And the second member, from the N-terminus to the C-terminus, includes the sdABD-TTA1-domain linker-sdABD-TTA2-aVL-CL-iVH-domain linker-sdABD-HSA.

The two sdABD-TTAs on each member of the pair are different, but generally both members (hemi-COBRAs ™) have the same two sdABD-TTAs, e.g. both EGFR and FOLR1 or EGFR and B7H3, etc. Have

The two sdABD-TTAs are, in some embodiments, selected from those shown in FIG. 5.

X. Method of making the composition of the present invention

The prodrug compositions of the present invention are generally recognized by those skilled in the art and are made as outlined below.

The present invention provides nucleic acid compositions encoding the prodrug compositions of the present invention. As will be appreciated by those skilled in the art, the nucleic acid composition will depend on the format of the prodrug polypeptide (s). Thus, for example, when such a format requires two amino acid sequences, such as a "Form 3" construct, two nucleic acid sequences can be incorporated into one or more expression vectors for expression. Similarly, a single polypeptide prodrug construct (forms 1, 2 and 4) requires a single nucleic acid in a single expression vector for production.

As is known in the art, nucleic acids encoding components of the invention can be incorporated into expression vectors as known in the art and depending on the host cell used to produce the prodrug composition of the invention. In general, these nucleic acids are operably linked to numerous regulatory elements (promoter, origin of replication, selectable markers, ribosome binding sites, inducers, etc.). The expression vector can be an extrachromosomal vector or an integrated vector.

Nucleic acid and / or expression vectors of the invention are then transformed into a number of different types of host cells as well known in the art, including mammalian, bacterial, yeast, insect and / or fungal cells, mammalian cells (e.g. For example, CHO cells, 293 cells) find use in many embodiments.

Prodrug compositions of the invention are made by culturing a host cell comprising expression vector (s), as is well known in the art. Once produced, traditional antibody purification steps are performed, including Protein A affinity chromatography steps and / or ion exchange chromatography steps.

XI. Formulation and administration of the prodrug composition of the present invention

Formulations of prodrug compositions used in accordance with the present invention are optionally pharmaceutically acceptable prodrugs (single protein for Forms 1, 2 and 4 and 2 proteins for Form 3) having a desired degree of purity. Prepared for storage in the form of a lyophilized formulation or aqueous solution, by mixing with a carrier, excipient or stabilizer (as outlined generally in Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. [1980]).

The prodrug compositions of the present invention are administered to a subject in a known manner, such as intravenous administration as bolus injections or by continuous infusion over a period of time.

The prodrug composition of the present invention is useful in the treatment of cancer.

XII. Example

A. Example 1: Construction and purification of precursor constructs

Transfection

Each protein (e.g., single protein in the case of types 1, 2 and 4) or a pair of constructs (type 3) was expressed from a separate expression vector (pcdna3.4 derivative). Equal amounts of plasmid DNA encoding a pair of hemi-cobra or single chain constructs were mixed and transfected into Expi293 cells according to the manufacturer's transfection protocol. Conditional medium was harvested 5 days after transfection by centrifugation (6000 rpm x 25 ') and filtration (0.2 uM filter). Protein expression was confirmed by SDS-PAGE. The construct was purified, and the final buffer composition was 25 mM citrate, 75 mM arginine, 75 mM NaCl, 4% sucrose, pH 7. The final product was stored at -80 ° C.

Activation of MMP9

Recombinant human (rh) MMP9 was activated according to the following protocol. Recombinant human MMP-9 (R & D # 911-MP-010) was 0.44 mg / ml (4.7 uM). p-aminophenylmercuric acetate (APMA) (Sigma) is prepared in DMSO at a stock concentration of 100 mM. Assay buffer was 50 mM Tris pH 7.5, 10 mM CaCl2, 150 mM NaCl, 0.05% Brij-35.

-Dilute rhMMP9 to ~ 100 ug / ml with assay buffer (25 ul hMMP9 + 75 uL assay buffer)

-Add p-aminophenylmercuric acetate (APMA) from 100 mM stock in DMSO to a final concentration of 1 mM (1 uL to 100 uL)

-Incubate at 37'C for 24 hours

-Dilute MMP9 to 10 ng / ul (900 ul of assay buffer is added to 100 ul of activated solution)

The concentration of activated rhMMP9 is ~ 100 nM.

Cleavage of constructs for TDCC assay

To cleave the construct, CaCl ₂ up to 10 mM in 100 ul protein samples at 1 mg / ml concentration (10.5 uM) in formulation buffer (25 mM citric acid, 75 mM L-arginine, 75 mM NaCl, 4% sucrose) Was supplied. Activated rhMMP9 was added to concentrations 20-35 nM. Specimens were incubated overnight at room temperature (16-20 hours). The completeness of cleavage was demonstrated using SDS PAGE (10-20% TG, TG working buffer, 200v, 1 hour). Samples were typically 98% cleaved.

B. Example 2: T cell dependent cell cytotoxicity (TDCC) assay

Firefly luciferase transduced HT-29 cells were grown to approximately 80% confluence and isolated with Versene (0.48 mM EDTA in PBS-Ca-Mg). Cells were centrifuged and resuspended in TDCC medium (HEPES, GlutaMax, sodium pyruvate, non-essential amino acids and 5% heat inactivated FBS in RPMI 1640 with β-mercaptoethanol). Purified human pan-T cells were thawed, centrifuged and resuspended in TDCC medium.

Co-cultures of HT-29_Luc cells and T cells were added to a 384-well cell culture plate. Series diluted COBRAs were then added to the co-culture and incubated at 37 ° C. for 48 hours. Finally, an equal volume of SteadyGlo luciferase assay reagent was added to the plate and incubated for 20 minutes. These plates were read at Perkin Elmer Envision with an exposure time of 0.1 s / well. Total luminescence was recorded, and data were analyzed in GraphPad Prism 7.

C. Example 3: General protocol design of in vivo adoptive T cell delivery efficacy model

These protocols were used in most of the experiments in the figure. Tumor cells are implanted subcutaneously (SC) in the right flank of NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl / SzJ) mice ( The Jackson Laboratory , catalog number 005557), and established tumors with an average volume of about 200 mm ³ are reached It was allowed to grow until. T cells in the culture medium in parallel with human T cells for about 10 days, T cell activation / expansion kit (Miltenyi catalog number 130-091-441) G-Rex100M gas permeable flask containing MACSiBeads (Wilson Wolf Cat. No. 81100S) from (X-VIVO 15 [ Lonza, Cat. No. 04-418Q], 5% human serum, 1% penicillin / streptomycin, 0.01 mM 2-mercaptoethanol) and supplemented with recombinant human IL-2 protein. Tumor growth in mouse and human T cell activation / expansion was organized so that mice were randomized into groups (N = 6) based on tumor size on day 0 of the study; Each was then injected intravenously (IV) with 2.5 × 10 ⁶ cultured human T cells and the first dose of COBRA or control molecule administered. Mice are dosed every 3 days for 7 doses (Days 0, 3, 6, 9, 12, 15 and 18), and then added until the tumor reaches> 2000 mm ³ in volume or the study is terminated. Followed for 2-3 weeks. Tumor volume was measured every 3 days.

D. Example 4: In vivo activity with EGFR / MMP9 hemi-cobra pair Pro77 and Pro53.

5 x 10 ⁶ LoVo cells or 5 x 10 ⁶ HT29 cells are implanted subcutaneously in the right flank of NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl / SzJ) mice ( The Jackson Laboratory , catalog number 005557), and until tumors are established Allowed to grow. T cells in the culture medium in parallel with human T cells for 10 days, T cell activation / expansion kit (Miltenyi catalog number 130-091-441) G-Rex100M gas permeable flask containing MACSiBeads (Wilson Wolf Cat. No. 81100S) from ( X-VIVO 15 [ Lonza, Cat. No. 04-418Q], 5% human serum, 1% penicillin / streptomycin, 0.01 mM 2-mercaptoethanol) and supplemented with recombinant human IL-2 protein. Tumor growth in mouse and human T cell activation / expansion was organized so that mice were randomized into groups (N = 6) based on tumor size on day 0 of the study; Each was then injected intravenously (IV) with 2.5 × 10 ⁶ cultured human T cells and the first dose of COBRA or control molecule administered. Mice are dosed every 3 days for 7 doses (Days 0, 3, 6, 9, 12, 15 and 18), and then followed until the tumor reaches> 2000 mm ³ in volume or the study is terminated. Became. The group was 0.2 mg / kg (mpk) anti-EGFR x CD3 positive control Pro51 bispecific antibody (bsAb), 0.5 mpk negative control anti-egg lysozyme (HEL) x CD3 bsAb Pro98, anti-EGFR hemi-COBRA pair A 0.5 mpk MMP9 cleavable linker each containing Pro77 and Pro53, or a 0.5 mpk non-cleavable (NCL) linker each containing anti-EGFR hemi-COBRA pair Pro74 and Pro72 was provided. Tumor volume was measured every 3 days.

E. Example 5: In vivo activity with EGFR / MMP9 COBRA Pro140.

5 x 10 ⁶ LoVo cells or 5 x 10 ⁶ HT29 cells are implanted subcutaneously in the right flank of NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl / SzJ) mice ( The Jackson Laboratory , catalog number 005557), and until tumors are established Allowed to grow. T cells in the culture medium in parallel with human T cells for 10 days, T cell activation / expansion kit (Miltenyi catalog number 130-091-441) G-Rex100M gas permeable flask containing MACSiBeads (Wilson Wolf Cat. No. 81100S) from ( X-VIVO 15 [ Lonza, Catalog No. 04-418Q], 5% human serum, 1% penicillin / streptomycin, 0.01 mM 2-mercaptoethanol) and supplemented with recombinant human IL-2 protein. Tumor growth in mouse and human T cell activation / expansion was organized so that mice were randomized into groups (N = 6) based on tumor size on day 0 of the study; Each was then injected intravenously (IV) with 2.5 × 10 ⁶ cultured human T cells and the first dose of COBRA or control molecule administered. Mice are dosed every 3 days for 7 doses (Days 0, 3, 6, 9, 12, 15 and 18), and then followed until the tumor reaches> 2000 mm ³ in volume or the study is terminated. Became. The group contains 0.2 mpk of anti-EGFR x CD3 positive control Pro51 bispecific antibody (bsAb), 0.5 mpk of negative control anti-egg lysozyme (HEL) x CD3 bsAb Pro98, or 0.5 mpk containing anti-EGFR COBRA Pro140. An MMP9 cleavable linker was provided. Tumor volume was measured every 3 days.

F. Example 6: In vivo activity with EGFR / MMP9 COBRA Pro186.

5 x 10 ⁶ HT29 cells were implanted subcutaneously in the right flank of NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl / SzJ) mice ( The Jackson Laboratory , catalog number 005557), and allowed to grow until the tumor was established. T cells in the culture medium in parallel with human T cells for 10 days, T cell activation / expansion kit (Miltenyi catalog number 130-091-441) G-Rex100M gas permeable flask containing MACSiBeads (Wilson Wolf Cat. No. 81100S) from ( X-VIVO 15 [ Lonza, Catalog No. 04-418Q], 5% human serum, 1% penicillin / streptomycin, 0.01 mM 2-mercaptoethanol) and supplemented with recombinant human IL-2 protein. Tumor growth in mouse and human T cell activation / expansion was organized so that mice were randomized into groups (N = 6) based on tumor size on day 0 of the study; Each was then injected intravenously (IV) with 2.5 × 10 ⁶ cultured human T cells and the first dose of COBRA or control molecule administered. Mice are dosed every 3 days for 7 doses (Days 0, 3, 6, 9, 12, 15 and 18), and then followed until the tumor reaches> 2000 mm ³ in volume or the study is terminated. Became. The group contains 0.1 mg / kg (mpk) anti-EGFR x CD3 positive control Pro51 bispecific antibody (bsAb), 0.3 mpk non-cleavable (NCL) control linker containing anti-EGFR COBRA Pro214, anti-EGFR COBRA A 0.1 or 0.3 mpk MMP9 cleavable linker containing Pro140, or a 0.1 or 0.3 mpk MMP9 cleavable linker containing anti-EGFR COBRA Pro186 was provided. Tumor volume was measured every 3 days.

G. Example: Successful humanization of anti-EGFR sequences

The results are shown below.

These results demonstrate that humanization of the EGFR binding domain was successful, as well as strong binding capacity to the target EGFR when two binding sites are on the molecule.

Example: Successful humanization of EpCAM sdABDs

The results are shown below.

These results demonstrate that humanization of the EpCAM binding domain was successful.

                         SEQUENCE LISTING <110> MAVERICK THERAPEUTICS, INC.   <120> CONSTRAINED CONDITIONALLY ACTIVATED BINDING PROTEINS <130> 118459-5005 <150> 62 / 555,943 <151> 2017-09-08 <150> 62 / 586,627 <151> 2017-11-15 <150> 62 / 587,318 <151> 2017-11-16 <160> 272 <170> PatentIn version 3.5 <210> 1 <211> 127 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-alpha-EGFR1 <400> 1 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr             20 25 30 Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Met Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr             100 105 110 Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser         115 120 125 <210> 2 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-alpha-EGFR1 <400> 2 Gly Arg Thr Phe Ser Ser Tyr Ala Met Gly 1 5 10 <210> 3 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-alpha-EGFR1 <400> 3 Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 <210> 4 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3-Targeting sdAbs-alpha-EGFR1 <400> 4 Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr Glu Tyr 1 5 10 15 Asp Tyr          <210> 5 <211> 124 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-alpha-EGFR2 <400> 5 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser         115 120 <210> 6 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-alpha-EGFR2 <400> 6 Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly 1 5 10 <210> 7 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-alpha-EGFR2 <400> 7 Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly      <210> 8 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-alpha-EGFR2 <400> 8 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr 1 5 10 15 <210> 9 <211> 127 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-h-alpha-EGFR1 <400> 9 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr             20 25 30 Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr             100 105 110 Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         115 120 125 <210> 10 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-h-alpha-EGFR1 <400> 10 Gly Arg Thr Phe Ser Ser Tyr Ala Met Gly 1 5 10 <210> 11 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-h-alpha-EGFR1 <400> 11 Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 <210> 12 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-h-alpha-EGFR1 <400> 12 Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr Glu Tyr 1 5 10 15 Asp Tyr          <210> 13 <211> 124 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-h-alpha-EGFR2 <400> 13 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         115 120 <210> 14 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-h-alpha-EGFR2 <400> 14 Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly 1 5 10 <210> 15 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-h-alpha-EGFR2 <400> 15 Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly      <210> 16 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-h-alpha-EGFR2 <400> 16 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr 1 5 10 15 <210> 17 <211> 114 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-alpha-FOLR1        h77-2 <400> 17 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser          <210> 18 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-alpha-FOLR1 h77-2 <400> 18 Gly Phe Thr Val Ser Asn Ser Val Met Ala 1 5 10 <210> 19 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-alpha-FOLR1 h77-2 <400> 19 Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 <210> 20 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-alpha-FOLR1 h77-2 <400> 20 Asn Phe Asp Arg Ile Tyr 1 5 <210> 21 <211> 113 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-alpha-FOLR1        h59.3 <400> 21 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser             20 25 30 Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val         35 40 45 Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys                 85 90 95 His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             100 105 110 Ser      <210> 22 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-alpha-FOLR1 h59.3 <400> 22 Gly Asn Thr Phe Ser Ile Ser Ala Met Gly 1 5 10 <210> 23 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-alpha-FOLR1 h59.3 <400> 23 Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 <210> 24 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-alpha-FOLR1 h59.3 <400> 24 Tyr Gly Ile Asp Tyr 1 5 <210> 25 <211> 117 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-alpha-FOLR1        h22-4 <400> 25 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu             100 105 110 Val Thr Val Ser Ser         115 <210> 26 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-alpha-FOLR1 h22-4 <400> 26 Gly Thr Thr Phe Ser Arg Asp Val Met Gly 1 5 10 <210> 27 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-alpha-FOLR1 h22-4 <400> 27 Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 <210> 28 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-alpha-FOLR1 h22-4 <400> 28 Asn Thr Ala Thr Trp Gly Arg Val Phe 1 5 <210> 29 <211> 124 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-alpha-B7H3        hF7 <400> 29 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr             20 25 30 His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         115 120 <210> 30 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-alpha-B7H3 hF7 <400> 30 Arg Arg Thr Phe His Thr Tyr His Met Gly 1 5 10 <210> 31 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-alpha-B7H3 hF7 <400> 31 Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly      <210> 32 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-alpha-B7H3 hF7 <400> 32 Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr 1 5 10 15 <210> 33 <211> 122 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-alpha-B7H3        hF12 <400> 33 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr             20 25 30 Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val         35 40 45 Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser         115 120 <210> 34 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-alpha-B7H3 hF12 <400> 34 Pro Arg Thr Phe Ser Thr Tyr Ser Met Ala 1 5 10 <210> 35 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-alpha-B7H3 hF12 <400> 35 Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys 1 5 10 15 Gly      <210> 36 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-alpha-B7H3 hF12 <400> 36 Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr 1 5 10 <210> 37 <211> 122 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-alpha-EpCAM        h13 <400> 37 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser         115 120 <210> 38 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-alpha-EpCAM h13 <400> 38 Gly Thr Gly Ser Ile Phe Ser Ile Asn Leu Met Gly 1 5 10 <210> 39 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-alpha-EpCAM h13 <400> 39 Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 <210> 40 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-alpha-EpCAM h13 <400> 40 Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr 1 5 10 <210> 41 <211> 122 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain -Targeting sdAbs-alpha-EpCAM        h23 <400> 41 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser         115 120 <210> 42 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1 -Targeting sdAbs-alpha-EpCAM h23 <400> 42 Gly Ser Phe Ser Ala Leu Trp Ala Met Arg 1 5 10 <210> 43 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2 -Targeting sdAbs-alpha-EpCAM h23 <400> 43 Ser Ser Arg Gly Gly Thr Thr Ser Tyr Ala Asp Ser Val Lys Gly 1 5 10 15 <210> 44 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3 -Targeting sdAbs-alpha-EpCAM h23 <400> 44 Ile Asp Gly His Leu Ala Tyr 1 5 <210> 45 <211> 115 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain-alpha-HSA half life extension        domain <400> 45 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe             20 25 30 Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         35 40 45 Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr             100 105 110 Val Ser Ser         115 <210> 46 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR1-alpha-HSA half-life extension domain <400> 46 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser 1 5 10 <210> 47 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR2-alpha-HSA half-life extension domain <400> 47 Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys 1 5 10 15 Gly      <210> 48 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic sdCDR3-alpha-HSA half-life extension domain <400> 48 Gly Gly Ser Leu Ser Val 1 5 <210> 49 <211> 109 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain-alpha-CD3 scFv Domain-        alpha-CD3V (L) <400> 49 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 1 5 10 15 Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly             20 25 30 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly         35 40 45 Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe     50 55 60 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val 65 70 75 80 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn                 85 90 95 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu             100 105 <210> 50 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetic aVLCDR1-alpha CD3 scFV Domain-alpha-CD3 V (L) <400> 50 Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn 1 5 10 <210> 51 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic aVLsdCDR2-alpha CD3 scFV Domain-alpha-CD3 V (L) <400> 51 Gly Thr Lys Phe Leu Val Pro 1 5 <210> 52 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic aVLsdCDR3-alpha CD3 scFV Domain-alpha-CD3 V (L) <400> 52 Thr Leu Trp Tyr Ser Asn Arg Trp Val 1 5 <210> 53 <211> 110 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain-alpha-CD3 scFv Domain-        alpha-CD3V (Li) <400> 53 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 1 5 10 15 Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly             20 25 30 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly         35 40 45 Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg     50 55 60 Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly 65 70 75 80 Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser                 85 90 95 Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu             100 105 110 <210> 54 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVLCDR1-alpha CD3 scFV Domain-alpha-CD3 V (Li) <400> 54 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn 1 5 10 <210> 55 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVLsdCDR2-alpha CD3 scFV Domain-alpha-CD3 V (Li) <400> 55 Asp Tyr Lys Asp Asp Asp Asp Lys 1 5 <210> 56 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVLsdCDR3-alpha CD3 scFV Domain-alpha-CD3 V (Li) <400> 56 Val Leu Trp Tyr Ser Asn Arg Trp Val 1 5 <210> 57 <211> 109 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain-alpha-CD3 scFv Domain-        alpha-CD3V (Li2) <400> 57 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 1 5 10 15 Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly             20 25 30 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly         35 40 45 Leu Ile Gly Gly Thr Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe     50 55 60 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val 65 70 75 80 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn                 85 90 95 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu             100 105 <210> 58 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVLCDR1-alpha CD3 scFV Domain-alpha-CD3 V (Li2) <400> 58 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn 1 5 10 <210> 59 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVLCDR2-alpha CD3 scFV Domain-alpha-CD3 V (Li2) <400> 59 Gly Thr Lys Asp Asp Ala Pro 1 5 <210> 60 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVLCDR3-alpha CD3 scFV Domain-alpha-CD3 V (Li2) <400> 60 Val Leu Trp Tyr Ser Asn Arg Trp Val 1 5 <210> 61 <211> 125 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain-alpha-CD3 scFv Domain-        alpha-CD3V (H) <400> 61 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             20 25 30 Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         35 40 45 Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp     50 55 60 Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 85 90 95 Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             100 105 110 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         115 120 125 <210> 62 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic aVHCDR1-alpha CD3 scFV Domain-alpha-CD3 V (H) <400> 62 Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn 1 5 10 <210> 63 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetic aVHsdCDR2-alpha CD3 scFV Domain-alpha-CD3 V (H) <400> 63 Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln 1 5 10 15 Val Lys Asp              <210> 64 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetic aVHsdCDR3-alpha CD3 scFV Domain-alpha-CD3 V (H) <400> 64 His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr 1 5 10 <210> 65 <211> 126 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain-alpha-CD3 scFv Domain-        alpha-CD3V (Hi) <400> 65 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             20 25 30 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         35 40 45 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     50 55 60 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 65 70 75 80 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 85 90 95 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             100 105 110 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         115 120 125 <210> 66 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVHsdCDR1-alpha CD3 scFV Domain-alpha-CD3 V (Hi) <400> 66 Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn 1 5 10 <210> 67 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVHsdCDR2-alpha CD3 scFV Domain-alpha-CD3 V (Hi) <400> 67 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp 1 5 10 15 Ser Val Lys Asp             20 <210> 68 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVHsdCDR3-alpha CD3 scFV Domain-alpha-CD3 V (Hi) <400> 68 His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr 1 5 10 <210> 69 <211> 125 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain-alpha-CD3 scFv Domain-        alpha-CD3V (Hi2) <400> 69 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys His             20 25 30 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         35 40 45 Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp     50 55 60 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 85 90 95 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             100 105 110 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         115 120 125 <210> 70 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVHsdCDR1-alpha CD3 scFV Domain-alpha-CD3 V (Hi2) <400> 70 Gly Phe Thr Phe Asn Lys His Ala Met Asn 1 5 10 <210> 71 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVHsdCDR2-alpha CD3 scFV Domain-alpha-CD3 V (Hi2) <400> 71 Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp Ser 1 5 10 15 Val Lys Asp              <210> 72 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetic iVHsdCDR3-alpha CD3 scFV Domain-alpha-CD3 V (Hi2) <400> 72 His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr 1 5 10 <210> 73 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetic linker-alpha-CD3 scFV-Normal, non-cleavable <400> 73 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15 <210> 74 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic linker-alpha-CD3 scFV-Constrained <400> 74 Gly Gly Gly Ser Gly Gly Gly Ser 1 5 <210> 75 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-MMP 2/9 <400> 75 Gly Pro Ala Gly Met Lys Gly Leu 1 5 <210> 76 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-MMP 2/9 <400> 76 Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser 1 5 10 15 <210> 77 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-MMP 2/9 <400> 77 Ser Gly Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Gly 1 5 10 15 Ser      <210> 78 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Meprin A / B <400> 78 Gly Gly Gly Gly Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser 1 5 10 15 <210> 79 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Meprin A / B <400> 79 Lys Lys Leu Ala Asp Glu Pro Glu 1 5 <210> 80 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Meprin A / B (Variant, high        efficiency) <400> 80 Gly Gly Gly Lys Phe Leu Ala Asp Glu Pro Glu Gly Gly 1 5 10 <210> 81 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Cathepsin S, K, L <400> 81 Ser Gly Gly Gly Ala Arg Leu Gln Ser Ala Ala Pro Gly Gly Gly Ser 1 5 10 15 <210> 82 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Cathepsin S, K, L <400> 82 Ala Arg Leu Gln Ser Ala Ala Pro 1 5 <210> 83 <211> 18 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Meprin / Granzyme B <400> 83 Ser Gly Gly Gly Gly Val Tyr Ala Asp Ser Leu Glu Asp Gly Gly Gly 1 5 10 15 Gly Ser          <210> 84 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Meprin / Granzyme B <400> 84 Gly Val Tyr Ala Asp Ser Leu Glu Asp Gly 1 5 10 <210> 85 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Matriptase / uPA (MS) <400> 85 Gly Gly Gly Ser Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser 1 5 10 15 <210> 86 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Matriptase / uPA (MS) <400> 86 Gly Leu Ser Gly Arg Ser Asp Asn His Gly 1 5 10 <210> 87 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Matriptase (MV) <400> 87 Ser Gly Gly Gly Ser Phe Thr Arg Gln Ala Arg Val Val Gly Gly Gly 1 5 10 15 Ser      <210> 88 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Matriptase (MV) <400> 88 Ser Phe Thr Arg Gln Ala Arg Val Val 1 5 <210> 89 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-CathepsinS / MMP9 / Meprin A <400> 89 Ala Arg Leu Gln Ser Ala Ala Pro Ala Gly Leu Lys Gly Ala 1 5 10 <210> 90 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-MMP9 (Variant, high efficiency) <400> 90 Gly Gly Pro Gly Pro Ala Gly Met His Gly Leu Pro Gly 1 5 10 <210> 91 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-MMP9 (Variant, low efficiency) <400> 91 Gly Gly Pro Gly Pro Ala Gly Met Glu Gly Leu Pro Gly 1 5 10 <210> 92 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Thrombin 1 <400> 92 Gly Gly Gly Gly Leu Val Pro Arg Gly Ser Leu Gly Gly Gly Gly Ser 1 5 10 15 <210> 93 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Thrombin 2 <400> 93 Ser Ser Gly Gly Gly Met Pro Arg Ser Phe Arg Gly Gly Gly Ser 1 5 10 15 <210> 94 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-Enterokinase / Flag <400> 94 Gly Gly Gly Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Gly Gly Ser 1 5 10 15 <210> 95 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-KLK7-6 <400> 95 Ser Gly Gly Gly Gln Asn Pro Tyr Ser Ala Gly Arg Gly Gly Gly Ser 1 5 10 15 <210> 96 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-KLK7-13 <400> 96 Ser Gly Gly Gly Gln Asn Pro Tyr Ser Ala Gly Gly Gly Ser Gly Gly 1 5 10 15 <210> 97 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-KLK7-11 <400> 97 Ser Gly Gly Gly Arg Asn Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly 1 5 10 15 <210> 98 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-KLK7-10 <400> 98 Ser Gly Gly Gly Gln Asn Thr Trp Ser Ala Gly Lys Gly Gly Gly Ser 1 5 10 15 <210> 99 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-uPA <400> 99 Gly Gly Gly Ser His Thr Gly Arg Ser Ala Tyr Phe Gly Gly Gly Ser 1 5 10 15 <210> 100 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP7 <400> 100 Lys Arg Ala Leu Gly Leu Pro Gly 1 5 <210> 101 <211> 24 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP7 <220> <221> misc_feature <222> (1) .. (8) <223> X can be Asp or Glu <220> <221> misc_feature <222> (17) .. (24) <223> X can be Asp or Arg <400> 101 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Arg Pro Leu Ala Leu Trp Arg Ser 1 5 10 15 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa             20 <210> 102 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP9 <400> 102 Pro Arg Ser Thr Leu Ile Ser Thr 1 5 <210> 103 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP9 <400> 103 Leu Glu Ala Thr Ala 1 5 <210> 104 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP11 <400> 104 Gly Gly Ala Ala Asn Leu Val Arg Gly Gly 1 5 10 <210> 105 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP14 <400> 105 Ser Gly Arg Ile Gly Phe Leu Arg Thr Ala 1 5 10 <210> 106 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP <400> 106 Pro Leu Gly Leu Ala Gly 1 5 <210> 107 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP <220> <221> misc_feature <222> (6) .. (6) <223> Xaa can be any naturally occurring amino acid <400> 107 Pro Leu Gly Leu Ala Xaa 1 5 <210> 108 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP <220> <221> misc_feature <222> (5) .. (5) <223> X can be Met or Glu <400> 108 Pro Leu Gly Cys Xaa Ala Gly 1 5 <210> 109 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP <400> 109 Glu Ser Pro Ala Tyr Tyr Thr Ala 1 5 <210> 110 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP <400> 110 Arg Leu Gln Leu Lys Leu 1 5 <210> 111 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP <400> 111 Arg Leu Gln Leu Lys Ala Cys 1 5 <210> 112 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-MMP2, MMP9, MMP14 <220> <221> misc_feature <222> (1) .. (3) <223> X can be Cys or Ile or Thr <220> <221> misc_feature <222> (5) .. (5) <223> X can be His or Orn or Phe <400> 112 Glu Pro Xaa Gly Xaa Tyr Leu 1 5 <210> 113 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Urokinase plasminogen        activator (upa) <400> 113 Ser Gly Arg Ser Ala 1 5 <210> 114 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Urokinase plasminogen        activator (upa) <400> 114 Asp Ala Phe Lys One <210> 115 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Urokinase plasminogen        activator (upa) <400> 115 Gly Gly Gly Arg Arg 1 5 <210> 116 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Lysosomal enzyme <400> 116 Gly Phe Leu Gly One <210> 117 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Lysosomal enzyme <400> 117 Ala Leu Ala Leu One <210> 118 <211> 2 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Lysosomal enzyme <400> 118 Phe Lys One <210> 119 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Cathepsin B <400> 119 Asn Leu Leu One <210> 120 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Cathepsin D <220> <221> misc_feature <222> (4) .. (4) <223> X can be Glu or Thr <400> 120 Pro Ile Cys Xaa Phe Phe 1 5 <210> 121 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Cathepsin K <400> 121 Gly Gly Pro Arg Gly Leu Pro Gly 1 5 <210> 122 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Prostate specific antigen <400> 122 His Ser Ser Lys Leu Gln 1 5 <210> 123 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Prostate specific antigen <400> 123 His Ser Ser Lys Leu Gln Leu 1 5 <210> 124 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Prostate specific antigen <400> 124 His Ser Ser Lys Leu Gln Glu Asp Ala 1 5 <210> 125 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Herpes simplex virus protease <400> 125 Leu Val Leu Ala Ser Ser Ser Phe Gly Tyr 1 5 10 <210> 126 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Hiv protease <400> 126 Gly Val Ser Gln Asn Tyr Pro Ile Val Gly 1 5 10 <210> 127 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Cmv protease <400> 127 Gly Val Val Gln Ala Ser Cys Arg Leu Ala 1 5 10 <210> 128 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Thrombin <220> <221> misc_feature <222> (2) .. (2) <223> X can be Pro or Ile or Pro <400> 128 Phe Xaa Arg Ser One <210> 129 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Thrombin <400> 129 Asp Pro Arg Ser Phe Leu 1 5 <210> 130 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Thrombin <400> 130 Pro Pro Arg Ser Phe Leu 1 5 <210> 131 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Caspase-3 <400> 131 Asp Glu Val Asp One <210> 132 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Caspase-3 <400> 132 Asp Glu Val Asp Pro 1 5 <210> 133 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Caspase-3 <400> 133 Lys Gly Ser Gly Asp Val Glu Gly 1 5 <210> 134 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Interleukin 1-beta converting        enzyme <400> 134 Gly Trp Glu His Asp Gly 1 5 <210> 135 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Enterokinase <400> 135 Glu Asp Asp Asp Asp Lys Ala 1 5 <210> 136 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Fap <400> 136 Lys Gln Glu Gln Asn Pro Gly Ser Thr 1 5 <210> 137 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Kallikrein 2 <400> 137 Gly Lys Ala Phe Arg Arg 1 5 <210> 138 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Plasmin <400> 138 Asp Ala Phe Lys One <210> 139 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Plasmin <400> 139 Asp Val Leu Lys One <210> 140 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Plasmin <400> 140 Asp Ala Phe Lys One <210> 141 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic protease cleavage site-Top <400> 141 Ala Leu Leu Leu Ala Leu Leu 1 5 <210> 142 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Synthetic antigen binding domain-alpha-HSA half life extension        domain <400> 142 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe             20 25 30 Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         35 40 45 Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr             100 105 110 Val Ser Ser His His His His His His         115 120 <210> 143 <211> 889 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro140 Format 1 <400> 143 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Pro Ala Gly Met Lys Gly Leu Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu 625 630 635 640 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser                 645 650 655 Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala             660 665 670 Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala         675 680 685 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp     690 695 700 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 705 710 715 720 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 725 730 735 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             740 745 750 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly         755 760 765 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly     770 775 780 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 785 790 795 800 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly                 805 810 815 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr             820 825 830 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         835 840 845 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp     850 855 860 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser 865 870 875 880 Gln Gly Thr Leu Val Thr Val Ser Ser                 885 <210> 144 <211> 890 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro140b Format 1 <400> 144 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Lys Lys Leu Ala Asp Glu Pro Glu Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys             500 505 510 Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 <210> 145 <211> 889 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro186 Format 2 <400> 145 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu 625 630 635 640 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser                 645 650 655 Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala             660 665 670 Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala         675 680 685 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp     690 695 700 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 705 710 715 720 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 725 730 735 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             740 745 750 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly         755 760 765 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly     770 775 780 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 785 790 795 800 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly                 805 810 815 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr             820 825 830 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         835 840 845 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp     850 855 860 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser 865 870 875 880 Gln Gly Thr Leu Val Thr Val Ser Ser                 885 <210> 146 <211> 890 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro187 Format 2 <400> 146 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys             500 505 510 Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 <210> 147 <211> 895 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro225 (FL aB7H3 hF7 MMP9 linker) Format 2 <400> 147 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr             20 25 30 His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val             420 425 430 Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 465 470 475 480 Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu 625 630 635 640 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser                 645 650 655 Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala             660 665 670 Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala         675 680 685 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp     690 695 700 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 705 710 715 720 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 725 730 735 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             740 745 750 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly         755 760 765 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly     770 775 780 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 785 790 795 800 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly                 805 810 815 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr             820 825 830 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         835 840 845 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp     850 855 860 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser 865 870 875 880 Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 148 <211> 891 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro226 (FL aB7H3 hF12 MMP9 linker) Format 2 <400> 148 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr             20 25 30 Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val         35 40 45 Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             260 265 270 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser         275 280 285 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     290 295 300 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val 305 310 315 320 Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 325 330 335 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             340 345 350 Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         355 360 365 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu     370 375 380 Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 385 390 395 400 Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr Ser Met Ala Trp                 405 410 415 Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val Ala Ala Ile Asn             420 425 430 Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe         435 440 445 Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn     450 455 460 Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Gly 465 470 475 480 Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr                 485 490 495 Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys             500 505 510 Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr         515 520 525 Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly     530 535 540 Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly 545 550 555 560 Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys                 565 570 575 Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala             580 585 590 Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys         595 600 605 Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu     610 615 620 Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val 625 630 635 640 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser                 645 650 655 Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val             660 665 670 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser         675 680 685 Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp     690 695 700 Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln 705 710 715 720 Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg                 725 730 735 His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly             740 745 750 Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly         755 760 765 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     770 775 780 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 785 790 795 800 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 805 810 815 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu             820 825 830 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr         835 840 845 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr     850 855 860 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu 865 870 875 880 Val Thr Val Ser Ser His His His His His His                 885 890 <210> 149 <211> 895 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro233 (humanized Pro186) Format 2 <400> 149 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu 625 630 635 640 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser                 645 650 655 Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala             660 665 670 Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala         675 680 685 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp     690 695 700 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 705 710 715 720 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 725 730 735 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             740 745 750 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly         755 760 765 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly     770 775 780 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 785 790 795 800 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly                 805 810 815 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr             820 825 830 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         835 840 845 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp     850 855 860 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser 865 870 875 880 Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 150 <211> 875 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro311 (FL aFOLR1 h77.2 MMP9 linker) Format        2 <400> 150 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu         115 120 125 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys     130 135 140 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg 145 150 155 160 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys                 165 170 175 Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe             180 185 190 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         195 200 205 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala     210 215 220 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln                 245 250 255 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr             260 265 270 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn         275 280 285 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu     290 295 300 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser 305 310 315 320 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln                 325 330 335 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg             340 345 350 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser         355 360 365 Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     370 375 380 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 385 390 395 400 Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu                 405 410 415 Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala             420 425 430 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn         435 440 445 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val     450 455 460 Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr 465 470 475 480 Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys                 485 490 495 Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr             500 505 510 Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly         515 520 525 Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly     530 535 540 Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys 545 550 555 560 Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala                 565 570 575 Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys             580 585 590 Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu         595 600 605 Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val     610 615 620 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 625 630 635 640 Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val                 645 650 655 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser             660 665 670 Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp         675 680 685 Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln     690 695 700 Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg 705 710 715 720 His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly                 725 730 735 Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly             740 745 750 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro         755 760 765 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser     770 775 780 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu 785 790 795 800 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu                 805 810 815 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr             820 825 830 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr         835 840 845 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu     850 855 860 Val Thr Val Ser Ser His His His His His His 865 870 875 <210> 151 <211> 873 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro312 (FL aFOLR1 h59.3 MMP9 linker) <400> 151 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser             20 25 30 Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val         35 40 45 Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys                 85 90 95 His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             100 105 110 Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         115 120 125 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala     130 135 140 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr                 165 170 175 Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr             180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn         195 200 205 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn     210 215 220 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr                 245 250 255 Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val             260 265 270 Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr         275 280 285 Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile     290 295 300 Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly 305 310 315 320 Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro                 325 330 335 Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp             340 345 350 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly         355 360 365 Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln     370 375 380 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe 385 390 395 400 Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg                 405 410 415 Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp             420 425 430 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr         435 440 445 Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr     450 455 460 Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val 465 470 475 480 Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu                 485 490 495 Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser             500 505 510 Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val         515 520 525 Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala     530 535 540 Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr 545 550 555 560 Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr                 565 570 575 Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu             580 585 590 Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val         595 600 605 Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser     610 615 620 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala 625 630 635 640 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln                 645 650 655 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr             660 665 670 Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe         675 680 685 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn     690 695 700 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly 705 710 715 720 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly                 725 730 735 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser             740 745 750 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn         755 760 765 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe     770 775 780 Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 785 790 795 800 Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val                 805 810 815 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr             820 825 830 Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys         835 840 845 Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr     850 855 860 Val Ser Ser His His His His His His 865 870 <210> 152 <211> 881 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro313 (FL aFOLR1 h22.4 MMP9 linker) Format        2 <400> 152 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln         115 120 125 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys     130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile                 165 170 175 Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys             180 185 190 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu         195 200 205 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val     210 215 220 Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp 225 230 235 240 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly                 245 250 255 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro             260 265 270 Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr         275 280 285 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro     290 295 300 Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala 305 310 315 320 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser                 325 330 335 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr             340 345 350 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser 385 390 395 400 Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val 465 470 475 480 Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro                 485 490 495 Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr             500 505 510 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr         515 520 525 Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp     530 535 540 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr 545 550 555 560 Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 565 570 575 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             580 585 590 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe         595 600 605 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly     610 615 620 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 625 630 635 640 Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys                 645 650 655 Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp             660 665 670 Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys         675 680 685 Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys     690 695 700 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala 705 710 715 720 Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser                 725 730 735 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly             740 745 750 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly         755 760 765 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala     770 775 780 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala 785 790 795 800 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg                 805 810 815 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg             820 825 830 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro         835 840 845 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val     850 855 860 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His 865 870 875 880 His      <210> 153 <211> 898 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro246 (FL haEGFR1 / haEGFR2 heterologous        COBRA with MMP9 linker) <400> 153 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr             20 25 30 Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr             100 105 110 Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly         115 120 125 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     130 135 140 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser 145 150 155 160 Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro                 165 170 175 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn             180 185 190 Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser         195 200 205 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys     210 215 220 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly 225 230 235 240 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val                 245 250 255 Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val             260 265 270 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         275 280 285 Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     290 295 300 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly 305 310 315 320 Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 325 330 335 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             340 345 350 Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe         355 360 365 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly     370 375 380 Ser Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly 385 390 395 400 Gly Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser                 405 410 415 Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe             420 425 430 Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser         435 440 445 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu     450 455 460 Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr 465 470 475 480 Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr                 485 490 495 Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly             500 505 510 Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val         515 520 525 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu     530 535 540 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn 545 550 555 560 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp                 565 570 575 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser             580 585 590 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu         595 600 605 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val     610 615 620 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro                 645 650 655 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn             660 665 670 Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu         675 680 685 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp     690 695 700 Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser 705 710 715 720 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr                 725 730 735 Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile             740 745 750 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         755 760 765 Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser     770 775 780 Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala 785 790 795 800 Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln                 805 810 815 Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly             820 825 830 Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser         835 840 845 Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg     850 855 860 Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser 865 870 875 880 Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His                 885 890 895 His His          <210> 154 <211> 893 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro256 (FL haEpCAM VIB13 / haEGFR1        heterologous COBRA MMP9 linker) <400> 154 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             260 265 270 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser         275 280 285 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     290 295 300 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val 305 310 315 320 Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 325 330 335 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             340 345 350 Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         355 360 365 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Lys Leu     370 375 380 Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu Thr Leu 385 390 395 400 Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp                 405 410 415 Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser             420 425 430 Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe         435 440 445 Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn     450 455 460 Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala Ala Ala 465 470 475 480 Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly             500 505 510 Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser         515 520 525 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser     530 535 540 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys 545 550 555 560 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp                 565 570 575 Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln 625 630 635 640 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys                 645 650 655 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn             660 665 670 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile         675 680 685 Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val     690 695 700 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr 705 710 715 720 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys                 725 730 735 Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr             740 745 750 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser         755 760 765 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     770 775 780 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 785 790 795 800 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly                 805 810 815 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr             820 825 830 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys         835 840 845 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala     850 855 860 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly 865 870 875 880 Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 <210> 155 <211> 885 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro420 (FL aFOLR1 h77.2 / haEGFR1        heterologous COBRA MMP9 linker) <400> 155 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu         115 120 125 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys     130 135 140 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg 145 150 155 160 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys                 165 170 175 Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe             180 185 190 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         195 200 205 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala     210 215 220 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln                 245 250 255 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr             260 265 270 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn         275 280 285 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu     290 295 300 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser 305 310 315 320 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln                 325 330 335 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg             340 345 350 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser         355 360 365 Gly Gly Gly Ser Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val     370 375 380 Arg Pro Gly Gly Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr 385 390 395 400 Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu                 405 410 415 Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr             420 425 430 Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys         435 440 445 Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala     450 455 460 Leu Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu 465 470 475 480 Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser                 485 490 495 Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln             500 505 510 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr         515 520 525 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn     530 535 540 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu 545 550 555 560 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe                 565 570 575 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val             580 585 590 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn         595 600 605 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly     610 615 620 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 625 630 635 640 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe                 645 650 655 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys             660 665 670 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp         675 680 685 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg     690 695 700 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr 705 710 715 720 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn                 725 730 735 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr             740 745 750 Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu         755 760 765 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu     770 775 780 Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp 785 790 795 800 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser                 805 810 815 Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe             820 825 830 Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn         835 840 845 Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly     850 855 860 Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His 865 870 875 880 His His His His His                 885 <210> 156 <211> 885 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro421 (FL haEGFR1 / aFOLR1 h77.2        heterologous COBRA MMP9 linker) <400> 156 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser Val Met                 405 410 415 Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val Ala Ile             420 425 430 Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys Gly Arg         435 440 445 Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met     450 455 460 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn Arg Asn 465 470 475 480 Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser                 485 490 495 Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln             500 505 510 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr         515 520 525 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn     530 535 540 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu 545 550 555 560 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe                 565 570 575 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val             580 585 590 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn         595 600 605 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly     610 615 620 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 625 630 635 640 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe                 645 650 655 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys             660 665 670 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp         675 680 685 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg     690 695 700 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr 705 710 715 720 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn                 725 730 735 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr             740 745 750 Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu         755 760 765 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu     770 775 780 Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp 785 790 795 800 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser                 805 810 815 Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe             820 825 830 Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn         835 840 845 Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly     850 855 860 Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His 865 870 875 880 His His His His His                 885 <210> 157 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro393 (Pro186 S9 linker) <400> 157 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Ala Arg Leu Gln Ser             500 505 510 Ala Ala Pro Ala Gly Leu Lys Gly Ala Gly Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 158 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro394 (Pro186 ST14 (MV) linker) <400> 158 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Phe Thr             500 505 510 Arg Gln Ala Arg Val Val Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 159 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro395 (Pro186 CathS linker) <400> 159 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Ala Arg             500 505 510 Leu Gln Ser Ala Ala Pro Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 160 <211> 897 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro396 (Pro186 MMP9v linker) <400> 160 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Ser Gly Gly Pro Gly             500 505 510 Pro Ala Gly Met His Gly Leu Pro Gly Gly Ser Gln Thr Val Val Thr         515 520 525 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr     530 535 540 Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp 545 550 555 560 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr                 565 570 575 Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu             580 585 590 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp         595 600 605 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe     610 615 620 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly                 645 650 655 Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys             660 665 670 Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp         675 680 685 Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys     690 695 700 Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys 705 710 715 720 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala                 725 730 735 Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser             740 745 750 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly         755 760 765 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly     770 775 780 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala 785 790 795 800 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala                 805 810 815 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg             820 825 830 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg         835 840 845 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro     850 855 860 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val 865 870 875 880 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His                 885 890 895 His      <210> 161 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro429 (Pro186 Meprin / GranzymeB linker) <400> 161 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Val Tyr             500 505 510 Ala Asp Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 162 <211> 895 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro430 (Pro186 MMP9-2 linker) <400> 162 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Leu Lys Gly Ala Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu 625 630 635 640 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser                 645 650 655 Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala             660 665 670 Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala         675 680 685 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp     690 695 700 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 705 710 715 720 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 725 730 735 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             740 745 750 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly         755 760 765 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly     770 775 780 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 785 790 795 800 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly                 805 810 815 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr             820 825 830 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         835 840 845 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp     850 855 860 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser 865 870 875 880 Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 163 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro431 (Pro186 ST14 (MS) linker) <400> 163 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Leu Ser             500 505 510 Gly Arg Ser Asp Asn His Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 164 <211> 763 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro258 (Pro186 with a single aEGFR domain        and a central aHSA domain) <400> 164 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala Gly Met Lys     370 375 380 Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 385 390 395 400 Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe                 405 410 415 Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys             420 425 430 Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu         435 440 445 Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala     450 455 460 Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr 465 470 475 480 Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly             500 505 510 Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly         515 520 525 Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser     530 535 540 Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg 545 550 555 560 Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala                 565 570 575 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser             580 585 590 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr         595 600 605 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly     610 615 620 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly 625 630 635 640 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser                 645 650 655 Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro             660 665 670 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr         675 680 685 Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile     690 695 700 Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu 705 710 715 720 Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe                 725 730 735 Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu             740 745 750 Val Thr Val Ser Ser His His His His His His         755 760 <210> 165 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro221-Cleavable linker variant <400> 165 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Gln Asn             500 505 510 Pro Tyr Ser Ala Gly Arg Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 166 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro222-Cleavable linker variant <400> 166 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Gln Asn             500 505 510 Pro Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 167 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro223-Cleavable linker variant <400> 167 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Arg Asn             500 505 510 Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 168 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro224- Cleavable linker variant <400> 168 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Gln Asn             500 505 510 Thr Trp Ser Ala Gly Lys Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 169 <211> 898 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro254- Heterologous Format 2 <400> 169 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr Ala Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Val Ala             420 425 430 Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 465 470 475 480 Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr Glu Tyr                 485 490 495 Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly             500 505 510 Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val         515 520 525 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu     530 535 540 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn 545 550 555 560 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp                 565 570 575 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser             580 585 590 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu         595 600 605 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val     610 615 620 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro                 645 650 655 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn             660 665 670 Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu         675 680 685 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp     690 695 700 Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser 705 710 715 720 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr                 725 730 735 Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile             740 745 750 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         755 760 765 Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser     770 775 780 Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala 785 790 795 800 Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln                 805 810 815 Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly             820 825 830 Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser         835 840 845 Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg     850 855 860 Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser 865 870 875 880 Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His                 885 890 895 His His          <210> 170 <211> 893 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro255- Heterologous Format 2 <400> 170 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly             500 505 510 Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser         515 520 525 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser     530 535 540 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys 545 550 555 560 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp                 565 570 575 Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln 625 630 635 640 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys                 645 650 655 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn             660 665 670 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile         675 680 685 Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val     690 695 700 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr 705 710 715 720 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys                 725 730 735 Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr             740 745 750 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser         755 760 765 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     770 775 780 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 785 790 795 800 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly                 805 810 815 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr             820 825 830 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys         835 840 845 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala     850 855 860 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly 865 870 875 880 Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 <210> 171 <211> 902 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro262 <400> 171 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser             260 265 270 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly         275 280 285 Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly     290 295 300 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly 305 310 315 320 Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe                 325 330 335 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val             340 345 350 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn         355 360 365 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly     370 375 380 Ser Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser 385 390 395 400 Val Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg                 405 410 415 Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys             420 425 430 Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly         435 440 445 Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala     450 455 460 Lys Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr 465 470 475 480 Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr                 485 490 495 Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser             500 505 510 Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser         515 520 525 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly     530 535 540 Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly 545 550 555 560 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly                 565 570 575 Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg             580 585 590 Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly         595 600 605 Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser     610 615 620 Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly                 645 650 655 Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly             660 665 670 Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly         675 680 685 Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys     690 695 700 Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser 705 710 715 720 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys                 725 730 735 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly             740 745 750 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val         755 760 765 Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln     770 775 780 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg 785 790 795 800 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser                 805 810 815 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile             820 825 830 Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg         835 840 845 Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met     850 855 860 Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly 865 870 875 880 Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 895 His His His His His His             900 <210> 172 <211> 766 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro356-Format 4 <400> 172 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr             20 25 30 Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr             100 105 110 Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly         115 120 125 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     130 135 140 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser 145 150 155 160 Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro                 165 170 175 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn             180 185 190 Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser         195 200 205 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys     210 215 220 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly 225 230 235 240 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val                 245 250 255 Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val             260 265 270 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         275 280 285 Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     290 295 300 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly 305 310 315 320 Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 325 330 335 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             340 345 350 Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe         355 360 365 Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala     370 375 380 Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly 385 390 395 400 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala                 405 410 415 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala             420 425 430 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg         435 440 445 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg     450 455 460 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro 465 470 475 480 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val                 485 490 495 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser             500 505 510 Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val         515 520 525 Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala     530 535 540 Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln 545 550 555 560 Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly                 565 570 575 Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu             580 585 590 Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val         595 600 605 Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr     610 615 620 Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu 625 630 635 640 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys                 645 650 655 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg             660 665 670 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys         675 680 685 Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg     690 695 700 Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 705 710 715 720 Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His                 725 730 735 Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln             740 745 750 Gly Thr Leu Val Thr Val Ser Ser His His His His His His         755 760 765 <210> 173 <211> 763 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro359-Format 4 <400> 173 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr             20 25 30 His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala Gly Met Lys     370 375 380 Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 385 390 395 400 Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe                 405 410 415 Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys             420 425 430 Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu         435 440 445 Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala     450 455 460 Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr 465 470 475 480 Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly             500 505 510 Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly         515 520 525 Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser     530 535 540 Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg 545 550 555 560 Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala                 565 570 575 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser             580 585 590 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr         595 600 605 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly     610 615 620 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly 625 630 635 640 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser                 645 650 655 Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro             660 665 670 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr         675 680 685 Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile     690 695 700 Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu 705 710 715 720 Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe                 725 730 735 Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu             740 745 750 Val Thr Val Ser Ser His His His His His His         755 760 <210> 174 <211> 752 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro364-Format 4 <400> 174 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser             20 25 30 Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val         35 40 45 Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys                 85 90 95 His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             100 105 110 Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         115 120 125 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala     130 135 140 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr                 165 170 175 Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr             180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn         195 200 205 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn     210 215 220 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr                 245 250 255 Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val             260 265 270 Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr         275 280 285 Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile     290 295 300 Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly 305 310 315 320 Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro                 325 330 335 Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp             340 345 350 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly         355 360 365 Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu     370 375 380 Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys 385 390 395 400 Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg                 405 410 415 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser             420 425 430 Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile         435 440 445 Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu     450 455 460 Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu 465 470 475 480 Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly                 485 490 495 Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu             500 505 510 Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr         515 520 525 Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro     530 535 540 Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp 545 550 555 560 Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 565 570 575 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             580 585 590 Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         595 600 605 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     610 615 620 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu 625 630 635 640 Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp                 645 650 655 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg             660 665 670 Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys         675 680 685 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu     690 695 700 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val 705 710 715 720 Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp                 725 730 735 Gly Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His             740 745 750 <210> 175 <211> 753 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro388-Format 4 <400> 175 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu         115 120 125 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys     130 135 140 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg 145 150 155 160 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys                 165 170 175 Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe             180 185 190 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         195 200 205 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala     210 215 220 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln                 245 250 255 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr             260 265 270 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn         275 280 285 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu     290 295 300 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser 305 310 315 320 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln                 325 330 335 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg             340 345 350 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly Pro         355 360 365 Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val     370 375 380 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser 385 390 395 400 Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val                 405 410 415 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly             420 425 430 Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr         435 440 445 Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser     450 455 460 Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser 465 470 475 480 Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly                 485 490 495 Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             500 505 510 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser         515 520 525 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     530 535 540 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp 545 550 555 560 Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys                 565 570 575 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr             580 585 590 Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr         595 600 605 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln     610 615 620 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys 625 630 635 640 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn                 645 650 655 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile             660 665 670 Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val         675 680 685 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr     690 695 700 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys 705 710 715 720 Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr                 725 730 735 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His             740 745 750 His      <210> 176 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro432- Heterologous-Format 2 <400> 176 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             260 265 270 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser         275 280 285 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     290 295 300 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val 305 310 315 320 Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 325 330 335 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             340 345 350 Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         355 360 365 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     370 375 380 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 385 390 395 400 Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr Ala Met Gly Trp                 405 410 415 Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Val Ala Ile Asn             420 425 430 Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe         435 440 445 Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn     450 455 460 Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Tyr 465 470 475 480 Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr Glu Tyr Asp Tyr                 485 490 495 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly             500 505 510 Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 177 <211> 636 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro448- Dual Targeting Hemis Format 3 <400> 177 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Lys Leu Val         115 120 125 Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu Thr Leu Ser     130 135 140 Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe 145 150 155 160 Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp                 165 170 175 Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr             180 185 190 Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser         195 200 205 Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala Ala Ala Gly     210 215 220 Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser                 245 250 255 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly             260 265 270 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr         275 280 285 Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val     290 295 300 Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 305 310 315 320 Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr                 325 330 335 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr             340 345 350 Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp         355 360 365 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly     370 375 380 Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val 385 390 395 400 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu                 405 410 415 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn             420 425 430 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp         435 440 445 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser     450 455 460 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu 465 470 475 480 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val                 485 490 495 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly             500 505 510 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln         515 520 525 Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe     530 535 540 Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 545 550 555 560 Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala                 565 570 575 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr             580 585 590 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val         595 600 605 Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr     610 615 620 Leu Val Thr Val Ser Ser His His His His His His 625 630 635 <210> 178 <211> 636 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro449 Dual Targeting Hemis Format 3 <400> 178 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly         115 120 125 Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu     130 135 140 Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 145 150 155 160 Thr Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn                 165 170 175 Glu Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr             180 185 190 Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys         195 200 205 Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala     210 215 220 Val Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser                 245 250 255 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly             260 265 270 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr         275 280 285 Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val     290 295 300 Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 305 310 315 320 Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr                 325 330 335 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr             340 345 350 Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp         355 360 365 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly     370 375 380 Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val 385 390 395 400 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu                 405 410 415 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn             420 425 430 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp         435 440 445 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser     450 455 460 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu 465 470 475 480 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val                 485 490 495 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly             500 505 510 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln         515 520 525 Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe     530 535 540 Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 545 550 555 560 Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala                 565 570 575 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr             580 585 590 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val         595 600 605 Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr     610 615 620 Leu Val Thr Val Ser Ser His His His His His His 625 630 635 <210> 179 <211> 636 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro450 Dual Targeting Hemis Format 3 <400> 179 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Lys Leu Val         115 120 125 Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu Thr Leu Ser     130 135 140 Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe 145 150 155 160 Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp                 165 170 175 Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr             180 185 190 Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser         195 200 205 Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala Ala Ala Gly     210 215 220 Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser                 245 250 255 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly             260 265 270 Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly         275 280 285 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly     290 295 300 Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe 305 310 315 320 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val                 325 330 335 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn             340 345 350 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly         355 360 365 Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu     370 375 380 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu 385 390 395 400 Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp                 405 410 415 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg             420 425 430 Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys         435 440 445 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu     450 455 460 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val 465 470 475 480 Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly             500 505 510 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln         515 520 525 Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe     530 535 540 Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 545 550 555 560 Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala                 565 570 575 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr             580 585 590 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val         595 600 605 Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr     610 615 620 Leu Val Thr Val Ser Ser His His His His His His 625 630 635 <210> 180 <211> 636 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro451 Dual Targeting Hemis Format 3 <400> 180 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly         115 120 125 Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu     130 135 140 Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 145 150 155 160 Thr Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn                 165 170 175 Glu Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr             180 185 190 Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys         195 200 205 Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala     210 215 220 Val Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser                 245 250 255 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly             260 265 270 Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly         275 280 285 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly     290 295 300 Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe 305 310 315 320 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val                 325 330 335 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn             340 345 350 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly         355 360 365 Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu     370 375 380 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu 385 390 395 400 Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp                 405 410 415 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg             420 425 430 Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys         435 440 445 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu     450 455 460 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val 465 470 475 480 Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly             500 505 510 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln         515 520 525 Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe     530 535 540 Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 545 550 555 560 Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala                 565 570 575 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr             580 585 590 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val         595 600 605 Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr     610 615 620 Leu Val Thr Val Ser Ser His His His His His His 625 630 635 <210> 181 <211> 893 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro479- Heterologous-Format 2 <400> 181 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr             20 25 30 His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr Ser Met                 405 410 415 Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val Ala Ala             420 425 430 Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 465 470 475 480 Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly             500 505 510 Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser         515 520 525 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser     530 535 540 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys 545 550 555 560 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp                 565 570 575 Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln 625 630 635 640 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys                 645 650 655 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn             660 665 670 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile         675 680 685 Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val     690 695 700 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr 705 710 715 720 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys                 725 730 735 Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr             740 745 750 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser         755 760 765 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     770 775 780 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 785 790 795 800 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly                 805 810 815 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr             820 825 830 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys         835 840 845 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala     850 855 860 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly 865 870 875 880 Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 <210> 182 <211> 893 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro480- Heterologous-Format 2 <400> 182 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr             20 25 30 Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val         35 40 45 Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             260 265 270 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser         275 280 285 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     290 295 300 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val 305 310 315 320 Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 325 330 335 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             340 345 350 Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         355 360 365 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu     370 375 380 Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 385 390 395 400 Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met Gly Trp                 405 410 415 Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val Ile Asn             420 425 430 Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly Arg Phe         435 440 445 Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn     450 455 460 Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Gly 465 470 475 480 Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly             500 505 510 Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser         515 520 525 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser     530 535 540 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys 545 550 555 560 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp                 565 570 575 Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln 625 630 635 640 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys                 645 650 655 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn             660 665 670 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile         675 680 685 Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val     690 695 700 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr 705 710 715 720 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys                 725 730 735 Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr             740 745 750 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser         755 760 765 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     770 775 780 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 785 790 795 800 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly                 805 810 815 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr             820 825 830 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys         835 840 845 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala     850 855 860 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly 865 870 875 880 Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 <210> 183 <211> 893 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro495-Format 2 <400> 183 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr             20 25 30 His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val             420 425 430 Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 465 470 475 480 Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp                 565 570 575 Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val 625 630 635 640 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu                 645 650 655 Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys His Ala Met             660 665 670 Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg         675 680 685 Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp Ser Val     690 695 700 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr 705 710 715 720 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys                 725 730 735 Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr             740 745 750 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser         755 760 765 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     770 775 780 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 785 790 795 800 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly                 805 810 815 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr             820 825 830 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys         835 840 845 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala     850 855 860 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly 865 870 875 880 Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 <210> 184 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetic cleavable linker-MMP9-2 <400> 184 Ser Gly Gly Pro Gly Pro Ala Gly Leu Lys Gly Ala Pro Gly Ser 1 5 10 15 <210> 185 <211> 887 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro141 <400> 185 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Pro Ala Gly Met Lys Gly Leu Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn                 565 570 575 Lys His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val 625 630 635 640 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu                 645 650 655 Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Ser Ala Met             660 665 670 Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg         675 680 685 Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp Ser Val     690 695 700 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr 705 710 715 720 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys                 725 730 735 Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Thr Phe Trp Ala Tyr             740 745 750 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser         755 760 765 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     770 775 780 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 785 790 795 800 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly                 805 810 815 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr             820 825 830 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys         835 840 845 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala     850 855 860 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly 865 870 875 880 Thr Leu Val Thr Val Ser Ser                 885 <210> 186 <211> 903 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro160 <400> 186 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Pro Ala Gly Met Lys Gly Leu Gly Gln Thr Val Val Thr             260 265 270 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr         275 280 285 Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp     290 295 300 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr 305 310 315 320 Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu                 325 330 335 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu             340 345 350 Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly         355 360 365 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser     370 375 380 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 385 390 395 400 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr                 405 410 415 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val             420 425 430 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val         435 440 445 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp     450 455 460 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys 465 470 475 480 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp                 485 490 495 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro             500 505 510 Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr         515 520 525 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr     530 535 540 Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp 545 550 555 560 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr                 565 570 575 Ser Asn Lys His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly                 645 650 655 Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala             660 665 670 Ser Gly Phe Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala         675 680 685 Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn     690 695 700 Asn Tyr Ala Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile 705 710 715 720 Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu                 725 730 735 Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe             740 745 750 Gly Asn Ser Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu         755 760 765 Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly     770 775 780 Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 785 790 795 800 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr                 805 810 815 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly             820 825 830 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr         835 840 845 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys     850 855 860 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 865 870 875 880 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly                 885 890 895 Thr Leu Val Thr Val Ser Ser             900 <210> 187 <211> 899 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro161 <400> 187 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Pro Ala Gly Met Lys Gly Leu Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly             500 505 510 Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser         515 520 525 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser     530 535 540 Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln Lys 545 550 555 560 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys His                 565 570 575 Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala             580 585 590 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr         595 600 605 Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr Lys     610 615 620 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val                 645 650 655 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr             660 665 670 Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly         675 680 685 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr     690 695 700 Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp 705 710 715 720 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp                 725 730 735 Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr             740 745 750 Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser         755 760 765 Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser     770 775 780 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn 785 790 795 800 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe                 805 810 815 Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val             820 825 830 Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val         835 840 845 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr     850 855 860 Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys 865 870 875 880 Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr                 885 890 895 Val Ser Ser              <210> 188 <211> 901 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro162 <400> 188 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Val Tyr Ala Asp Ser Leu Glu Asp Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Val Tyr Ala Asp             500 505 510 Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys                 565 570 575 His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala     690 695 700 Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp 705 710 715 720 Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu                 725 730 735 Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser             740 745 750 Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val         755 760 765 Ser Ser Gly Gly Gly Ser Val Tyr Ala Asp Ser Leu Glu Asp Gly Gly     770 775 780 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro 785 790 795 800 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser                 805 810 815 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu             820 825 830 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu         835 840 845 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr     850 855 860 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr 865 870 875 880 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu                 885 890 895 Val Thr Val Ser Ser             900 <210> 189 <211> 901 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro189 <400> 189 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Ala Arg Leu Gln Ser Ala Ala Pro Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Ala Arg Leu Gln             500 505 510 Ser Ala Ala Pro Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys                 565 570 575 His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala     690 695 700 Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp 705 710 715 720 Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu                 725 730 735 Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser             740 745 750 Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val         755 760 765 Ser Ser Gly Gly Gly Ser Ala Arg Leu Gln Ser Ala Ala Pro Gly Gly     770 775 780 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro 785 790 795 800 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser                 805 810 815 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu             820 825 830 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu         835 840 845 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr     850 855 860 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr 865 870 875 880 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu                 885 890 895 Val Thr Val Ser Ser             900 <210> 190 <211> 901 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro164 <400> 190 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Lys Lys Leu Ala Asp Glu Pro Glu Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala             500 505 510 Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys                 565 570 575 His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala     690 695 700 Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp 705 710 715 720 Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu                 725 730 735 Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser             740 745 750 Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val         755 760 765 Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly     770 775 780 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro 785 790 795 800 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser                 805 810 815 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu             820 825 830 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu         835 840 845 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr     850 855 860 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr 865 870 875 880 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu                 885 890 895 Val Thr Val Ser Ser             900 <210> 191 <211> 901 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro 191 <400> 191 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Leu Ser Gly Arg Ser Asp Asn His Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Leu Ser Gly Arg             500 505 510 Ser Asp Asn His Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys                 565 570 575 His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala     690 695 700 Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp 705 710 715 720 Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu                 725 730 735 Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser             740 745 750 Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val         755 760 765 Ser Ser Gly Gly Gly Ser Leu Ser Gly Arg Ser Asp Asn His Gly Gly     770 775 780 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro 785 790 795 800 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser                 805 810 815 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu             820 825 830 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu         835 840 845 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr     850 855 860 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr 865 870 875 880 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu                 885 890 895 Val Thr Val Ser Ser             900 <210> 192 <211> 901 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro166 <400> 192 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser                 245 250 255 Phe Thr Arg Gln Ala Arg Val Val Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Phe Thr Arg Gln             500 505 510 Ala Arg Val Val Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys                 565 570 575 His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala     690 695 700 Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp 705 710 715 720 Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu                 725 730 735 Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser             740 745 750 Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val         755 760 765 Ser Ser Gly Gly Gly Ser Phe Thr Arg Gln Ala Arg Val Val Gly Gly     770 775 780 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro 785 790 795 800 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser                 805 810 815 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu             820 825 830 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu         835 840 845 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr     850 855 860 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr 865 870 875 880 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu                 885 890 895 Val Thr Val Ser Ser             900 <210> 193 <211> 901 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro169 <400> 193 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Pro Ala Gly Met Lys Gly Leu Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly             500 505 510 Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser         515 520 525 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser     530 535 540 Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln Lys 545 550 555 560 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp                 565 570 575 Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp     690 695 700 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg 705 710 715 720 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr                 725 730 735 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn             740 745 750 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr         755 760 765 Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro     770 775 780 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro 785 790 795 800 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser                 805 810 815 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu             820 825 830 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu         835 840 845 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr     850 855 860 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr 865 870 875 880 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu                 885 890 895 Val Thr Val Ser Ser             900 <210> 194 <211> 903 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro170 <400> 194 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Val Tyr Ala Asp Ser Leu Glu Asp Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Val Tyr Ala Asp             500 505 510 Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp                 565 570 575 Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly                 645 650 655 Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly             660 665 670 Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly         675 680 685 Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys     690 695 700 Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser 705 710 715 720 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys                 725 730 735 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly             740 745 750 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val         755 760 765 Thr Val Ser Ser Gly Gly Gly Ser Val Tyr Ala Asp Ser Leu Glu Asp     770 775 780 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 785 790 795 800 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr                 805 810 815 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly             820 825 830 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr         835 840 845 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys     850 855 860 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 865 870 875 880 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly                 885 890 895 Thr Leu Val Thr Val Ser Ser             900 <210> 195 <211> 903 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro171 <400> 195 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Ala Arg Leu Gln Ser Ala Ala Pro Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Ala Arg Leu Gln             500 505 510 Ser Ala Ala Pro Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp                 565 570 575 Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly                 645 650 655 Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly             660 665 670 Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly         675 680 685 Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys     690 695 700 Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser 705 710 715 720 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys                 725 730 735 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly             740 745 750 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val         755 760 765 Thr Val Ser Ser Gly Gly Gly Ser Ala Arg Leu Gln Ser Ala Ala Pro     770 775 780 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 785 790 795 800 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr                 805 810 815 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly             820 825 830 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr         835 840 845 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys     850 855 860 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 865 870 875 880 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly                 885 890 895 Thr Leu Val Thr Val Ser Ser             900 <210> 196 <211> 903 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro172 <400> 196 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Lys Lys Leu Ala Asp Glu Pro Glu Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala             500 505 510 Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp                 565 570 575 Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly                 645 650 655 Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly             660 665 670 Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly         675 680 685 Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys     690 695 700 Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser 705 710 715 720 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys                 725 730 735 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly             740 745 750 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val         755 760 765 Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu     770 775 780 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 785 790 795 800 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr                 805 810 815 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly             820 825 830 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr         835 840 845 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys     850 855 860 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 865 870 875 880 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly                 885 890 895 Thr Leu Val Thr Val Ser Ser             900 <210> 197 <211> 903 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro173 <400> 197 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Leu Ser Gly Arg Ser Asp Asn His Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Leu Ser Gly Arg             500 505 510 Ser Asp Asn His Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp                 565 570 575 Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly                 645 650 655 Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly             660 665 670 Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly         675 680 685 Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys     690 695 700 Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser 705 710 715 720 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys                 725 730 735 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly             740 745 750 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val         755 760 765 Thr Val Ser Ser Gly Gly Gly Ser Leu Ser Gly Arg Ser Asp Asn His     770 775 780 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 785 790 795 800 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr                 805 810 815 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly             820 825 830 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr         835 840 845 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys     850 855 860 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 865 870 875 880 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly                 885 890 895 Thr Leu Val Thr Val Ser Ser             900 <210> 198 <211> 903 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro174 <400> 198 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser                 245 250 255 Phe Thr Arg Gln Ala Arg Val Val Gly Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn                 405 410 415 Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val             420 425 430 Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu     450 455 460 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn 465 470 475 480 Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Phe Thr Arg Gln             500 505 510 Ala Arg Val Val Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro         515 520 525 Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser     530 535 540 Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln 545 550 555 560 Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp                 565 570 575 Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly                 645 650 655 Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly             660 665 670 Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly         675 680 685 Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys     690 695 700 Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser 705 710 715 720 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys                 725 730 735 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly             740 745 750 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val         755 760 765 Thr Val Ser Ser Gly Gly Gly Ser Phe Thr Arg Gln Ala Arg Val Val     770 775 780 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 785 790 795 800 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr                 805 810 815 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly             820 825 830 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr         835 840 845 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys     850 855 860 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 865 870 875 880 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly                 885 890 895 Thr Leu Val Thr Val Ser Ser             900 <210> 199 <211> 888 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro176 <400> 199 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Pro Ala Gly Met Lys Gly Leu Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp                 565 570 575 Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val 625 630 635 640 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu                 645 650 655 Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met             660 665 670 Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg         675 680 685 Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser     690 695 700 Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala 705 710 715 720 Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr                 725 730 735 Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala             740 745 750 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly         755 760 765 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu     770 775 780 Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 785 790 795 800 Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys                 805 810 815 Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu             820 825 830 Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala         835 840 845 Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr     850 855 860 Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln 865 870 875 880 Gly Thr Leu Val Thr Val Ser Ser                 885 <210> 200 <211> 892 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro178 <400> 200 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Lys Lys Leu Ala Asp Glu Pro Glu Gly Gln Thr Val Val Thr             260 265 270 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr         275 280 285 Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp     290 295 300 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr 305 310 315 320 Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu                 325 330 335 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu             340 345 350 Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly         355 360 365 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser     370 375 380 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 385 390 395 400 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr                 405 410 415 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val             420 425 430 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val         435 440 445 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp     450 455 460 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys 465 470 475 480 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp                 485 490 495 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser             500 505 510 Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val         515 520 525 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu     530 535 540 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn 545 550 555 560 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp                 565 570 575 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser             580 585 590 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu         595 600 605 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val     610 615 620 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro                 645 650 655 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn             660 665 670 Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu         675 680 685 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp     690 695 700 Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser 705 710 715 720 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr                 725 730 735 Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile             740 745 750 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         755 760 765 Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser     770 775 780 Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala 785 790 795 800 Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln                 805 810 815 Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly             820 825 830 Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser         835 840 845 Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg     850 855 860 Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser 865 870 875 880 Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 <210> 201 <211> 894 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro179 <400> 201 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Ser Gln Thr Val             260 265 270 Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr         275 280 285 Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro     290 295 300 Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly 305 310 315 320 Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser                 325 330 335 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu             340 345 350 Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val         355 360 365 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly     370 375 380 Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr 385 390 395 400 Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg                 405 410 415 Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu             420 425 430 Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp         435 440 445 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr     450 455 460 Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr 465 470 475 480 Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu                 485 490 495 Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly             500 505 510 Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr         515 520 525 Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val     530 535 540 Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr 545 550 555 560 Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile                 565 570 575 Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser             580 585 590 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln         595 600 605 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg     610 615 620 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser 625 630 635 640 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val                 645 650 655 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr             660 665 670 Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly         675 680 685 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp     690 695 700 Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp 705 710 715 720 Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu                 725 730 735 Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser             740 745 750 Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val         755 760 765 Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val     770 775 780 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser 785 790 795 800 Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val                 805 810 815 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly             820 825 830 Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr         835 840 845 Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser     850 855 860 Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser 865 870 875 880 Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 <210> 202 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro180 <400> 202 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Ser Gln             260 265 270 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr         275 280 285 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn     290 295 300 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu 305 310 315 320 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser                 325 330 335 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln             340 345 350 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg         355 360 365 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser     370 375 380 Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val 385 390 395 400 Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr                 405 410 415 Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu             420 425 430 Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr         435 440 445 Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys     450 455 460 Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 465 470 475 480 Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu                 485 490 495 Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser             500 505 510 Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser         515 520 525 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly     530 535 540 Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly 545 550 555 560 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly                 565 570 575 Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg             580 585 590 Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly         595 600 605 Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser     610 615 620 Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly                 645 650 655 Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly             660 665 670 Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly         675 680 685 Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys     690 695 700 Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser 705 710 715 720 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys                 725 730 735 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly             740 745 750 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val         755 760 765 Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln     770 775 780 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg 785 790 795 800 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser                 805 810 815 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile             820 825 830 Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg         835 840 845 Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met     850 855 860 Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly 865 870 875 880 Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 895 <210> 203 <211> 898 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro181 <400> 203 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly             260 265 270 Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly         275 280 285 Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser     290 295 300 Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg 305 310 315 320 Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg                 325 330 335 Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly             340 345 350 Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser         355 360 365 Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly     370 375 380 Gly Ser Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly 385 390 395 400 Ser Val Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly                 405 410 415 Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly             420 425 430 Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr         435 440 445 Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn     450 455 460 Ala Lys Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp 465 470 475 480 Thr Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly                 485 490 495 Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val             500 505 510 Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly         515 520 525 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro     530 535 540 Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr 545 550 555 560 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro                 565 570 575 Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro             580 585 590 Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu         595 600 605 Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp     610 615 620 Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 625 630 635 640 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly                 645 650 655 Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala             660 665 670 Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala         675 680 685 Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp     690 695 700 Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr 705 710 715 720 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn                 725 730 735 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn             740 745 750 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr         755 760 765 Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu     770 775 780 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser 785 790 795 800 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly                 805 810 815 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser             820 825 830 Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys         835 840 845 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu     850 855 860 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr 865 870 875 880 Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val                 885 890 895 Ser Ser          <210> 204 <211> 891 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro182 <400> 204 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Pro Ala Gly Met Lys Gly Leu Gly Gln Thr Val Val Thr             260 265 270 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr         275 280 285 Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp     290 295 300 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr 305 310 315 320 Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu                 325 330 335 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu             340 345 350 Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly         355 360 365 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser     370 375 380 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 385 390 395 400 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr                 405 410 415 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val             420 425 430 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val         435 440 445 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp     450 455 460 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys 465 470 475 480 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp                 485 490 495 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro             500 505 510 Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr         515 520 525 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr     530 535 540 Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp 545 550 555 560 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr                 565 570 575 Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu             580 585 590 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp         595 600 605 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe     610 615 620 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly                 645 650 655 Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys             660 665 670 Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp         675 680 685 Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys     690 695 700 Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys 705 710 715 720 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala                 725 730 735 Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser             740 745 750 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly         755 760 765 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly     770 775 780 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala 785 790 795 800 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala                 805 810 815 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg             820 825 830 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg         835 840 845 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro     850 855 860 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val 865 870 875 880 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 <210> 205 <211> 893 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro183 <400> 205 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Ser Gly Pro Ala Gly Met Lys Gly Leu Gly Ser Gln Thr Val             260 265 270 Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr         275 280 285 Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro     290 295 300 Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly 305 310 315 320 Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser                 325 330 335 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu             340 345 350 Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val         355 360 365 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly     370 375 380 Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr 385 390 395 400 Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg                 405 410 415 Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu             420 425 430 Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp         435 440 445 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr     450 455 460 Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr 465 470 475 480 Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu                 485 490 495 Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly             500 505 510 Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val         515 520 525 Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr     530 535 540 Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro 545 550 555 560 Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly                 565 570 575 Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly             580 585 590 Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro         595 600 605 Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp     610 615 620 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly 625 630 635 640 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln                 645 650 655 Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe             660 665 670 Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu         675 680 685 Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp     690 695 700 Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp 705 710 715 720 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp                 725 730 735 Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr             740 745 750 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser         755 760 765 Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu     770 775 780 Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys 785 790 795 800 Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg                 805 810 815 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser             820 825 830 Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile         835 840 845 Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu     850 855 860 Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu 865 870 875 880 Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 <210> 206 <211> 895 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro184 <400> 206 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Ser Gly Pro Ala Gly Met Lys Gly Leu Gly Gly Ser Gln             260 265 270 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr         275 280 285 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn     290 295 300 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu 305 310 315 320 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser                 325 330 335 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln             340 345 350 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg         355 360 365 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser     370 375 380 Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val 385 390 395 400 Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr                 405 410 415 Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu             420 425 430 Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr         435 440 445 Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys     450 455 460 Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 465 470 475 480 Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu                 485 490 495 Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser             500 505 510 Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln         515 520 525 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr     530 535 540 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn 545 550 555 560 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu                 565 570 575 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe             580 585 590 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val         595 600 605 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn     610 615 620 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp     690 695 700 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg 705 710 715 720 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr                 725 730 735 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn             740 745 750 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr         755 760 765 Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     770 775 780 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu 785 790 795 800 Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp                 805 810 815 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser             820 825 830 Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe         835 840 845 Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn     850 855 860 Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly 865 870 875 880 Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 895 <210> 207 <211> 897 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro185 <400> 207 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Pro Ala Gly Met Lys Gly Leu Gly Gly Gly             260 265 270 Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly         275 280 285 Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser     290 295 300 Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg 305 310 315 320 Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg                 325 330 335 Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly             340 345 350 Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser         355 360 365 Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly     370 375 380 Gly Ser Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly 385 390 395 400 Ser Val Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly                 405 410 415 Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly             420 425 430 Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr         435 440 445 Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn     450 455 460 Ala Lys Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp 465 470 475 480 Thr Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly                 485 490 495 Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val             500 505 510 Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly         515 520 525 Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly     530 535 540 Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser 545 550 555 560 Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg                 565 570 575 Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala             580 585 590 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser         595 600 605 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr     610 615 620 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 625 630 635 640 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly                 645 650 655 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser             660 665 670 Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro         675 680 685 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr     690 695 700 Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile 705 710 715 720 Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu                 725 730 735 Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe             740 745 750 Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu         755 760 765 Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val     770 775 780 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu 785 790 795 800 Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met                 805 810 815 Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser             820 825 830 Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly         835 840 845 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln     850 855 860 Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile 865 870 875 880 Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser                 885 890 895 Ser      <210> 208 <211> 889 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro188 <400> 208 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Pro Ala Gly Met Lys Gly Leu Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu 625 630 635 640 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser                 645 650 655 Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala             660 665 670 Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala         675 680 685 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp     690 695 700 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 705 710 715 720 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 725 730 735 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             740 745 750 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly         755 760 765 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly     770 775 780 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 785 790 795 800 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly                 805 810 815 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr             820 825 830 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         835 840 845 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp     850 855 860 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser 865 870 875 880 Gln Gly Thr Leu Val Thr Val Ser Ser                 885 <210> 209 <211> 897 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro189 <400> 209 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly 625 630 635 640 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly                 645 650 655 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser             660 665 670 Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro         675 680 685 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr     690 695 700 Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile 705 710 715 720 Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu                 725 730 735 Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe             740 745 750 Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu         755 760 765 Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val     770 775 780 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu 785 790 795 800 Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met                 805 810 815 Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser             820 825 830 Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly         835 840 845 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln     850 855 860 Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile 865 870 875 880 Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser                 885 890 895 Ser      <210> 210 <211> 898 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro190 <400> 210 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys             500 505 510 Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly                 645 650 655 Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala             660 665 670 Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala         675 680 685 Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp     690 695 700 Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr 705 710 715 720 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn                 725 730 735 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn             740 745 750 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr         755 760 765 Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu     770 775 780 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser 785 790 795 800 Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly                 805 810 815 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser             820 825 830 Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys         835 840 845 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu     850 855 860 Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr 865 870 875 880 Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val                 885 890 895 Ser Ser          <210> 211 <211> 903 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro191 <400> 211 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly 625 630 635 640 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly                 645 650 655 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser             660 665 670 Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro         675 680 685 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr     690 695 700 Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile 705 710 715 720 Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu                 725 730 735 Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe             740 745 750 Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu         755 760 765 Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly     770 775 780 Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val 785 790 795 800 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr                 805 810 815 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly             820 825 830 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr         835 840 845 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys     850 855 860 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 865 870 875 880 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly                 885 890 895 Thr Leu Val Thr Val Ser Ser             900 <210> 212 <211> 905 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro192 <400> 212 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys             500 505 510 Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly                 645 650 655 Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala             660 665 670 Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala         675 680 685 Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp     690 695 700 Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr 705 710 715 720 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn                 725 730 735 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn             740 745 750 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr         755 760 765 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu     770 775 780 Pro Glu Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly 785 790 795 800 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly                 805 810 815 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly             820 825 830 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr         835 840 845 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn     850 855 860 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp 865 870 875 880 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser                 885 890 895 Gln Gly Thr Leu Val Thr Val Ser Ser             900 905 <210> 213 <211> 763 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro193 <400> 213 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala Gly Met Lys     370 375 380 Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 385 390 395 400 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe                 405 410 415 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys             420 425 430 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp         435 440 445 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg     450 455 460 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr 465 470 475 480 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn                 485 490 495 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr             500 505 510 Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr         515 520 525 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr     530 535 540 Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp 545 550 555 560 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr                 565 570 575 Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu             580 585 590 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp         595 600 605 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe     610 615 620 Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala 625 630 635 640 Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly                 645 650 655 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala             660 665 670 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala         675 680 685 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg     690 695 700 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 705 710 715 720 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro                 725 730 735 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val             740 745 750 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser         755 760 <210> 214 <211> 892 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro195 <400> 214 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr             20 25 30 Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Met Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr             100 105 110 Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly         115 120 125 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     130 135 140 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser 145 150 155 160 Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro                 165 170 175 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn             180 185 190 Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser         195 200 205 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys     210 215 220 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly 225 230 235 240 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val                 245 250 255 Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val             260 265 270 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         275 280 285 Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     290 295 300 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly 305 310 315 320 Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 325 330 335 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             340 345 350 Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe         355 360 365 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly     370 375 380 Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly 385 390 395 400 Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser                 405 410 415 Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe             420 425 430 Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser         435 440 445 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val     450 455 460 Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr 465 470 475 480 Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr                 485 490 495 Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly             500 505 510 Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val         515 520 525 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu     530 535 540 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn 545 550 555 560 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp                 565 570 575 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser             580 585 590 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu         595 600 605 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val     610 615 620 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro                 645 650 655 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn             660 665 670 Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu         675 680 685 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp     690 695 700 Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser 705 710 715 720 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr                 725 730 735 Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile             740 745 750 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         755 760 765 Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser     770 775 780 Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala 785 790 795 800 Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln                 805 810 815 Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly             820 825 830 Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser         835 840 845 Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg     850 855 860 Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser 865 870 875 880 Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 <210> 215 <211> 889 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro196 <400> 215 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val     130 135 140 Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala 145 150 155 160 Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln                 165 170 175 Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr             180 185 190 Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr         195 200 205 Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu     210 215 220 Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val 225 230 235 240 Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser                 245 250 255 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala             260 265 270 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln         275 280 285 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr     290 295 300 Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr 305 310 315 320 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn                 325 330 335 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn             340 345 350 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr         355 360 365 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu 625 630 635 640 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser                 645 650 655 Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala             660 665 670 Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala         675 680 685 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp     690 695 700 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 705 710 715 720 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 725 730 735 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             740 745 750 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly         755 760 765 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly     770 775 780 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 785 790 795 800 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly                 805 810 815 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr             820 825 830 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         835 840 845 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp     850 855 860 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser 865 870 875 880 Gln Gly Thr Leu Val Thr Val Ser Ser                 885 <210> 216 <211> 888 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro197 <400> 216 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser         515 520 525 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala     530 535 540 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln 545 550 555 560 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr                 565 570 575 Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe             580 585 590 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         595 600 605 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly     610 615 620 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 625 630 635 640 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln                 645 650 655 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr             660 665 670 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn         675 680 685 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu     690 695 700 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe 705 710 715 720 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val                 725 730 735 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn             740 745 750 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly         755 760 765 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu     770 775 780 Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 785 790 795 800 Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys                 805 810 815 Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu             820 825 830 Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala         835 840 845 Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr     850 855 860 Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln 865 870 875 880 Gly Thr Leu Val Thr Val Ser Ser                 885 <210> 217 <211> 888 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro198 <400> 217 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val     130 135 140 Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala 145 150 155 160 Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln                 165 170 175 Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr             180 185 190 Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr         195 200 205 Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu     210 215 220 Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val 225 230 235 240 Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser                 245 250 255 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala             260 265 270 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln         275 280 285 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr     290 295 300 Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr 305 310 315 320 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn                 325 330 335 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn             340 345 350 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr         355 360 365 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser         515 520 525 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala     530 535 540 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln 545 550 555 560 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr                 565 570 575 Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe             580 585 590 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         595 600 605 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly     610 615 620 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 625 630 635 640 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln                 645 650 655 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr             660 665 670 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn         675 680 685 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu     690 695 700 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe 705 710 715 720 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val                 725 730 735 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn             740 745 750 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly         755 760 765 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu     770 775 780 Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 785 790 795 800 Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys                 805 810 815 Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu             820 825 830 Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala         835 840 845 Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr     850 855 860 Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln 865 870 875 880 Gly Thr Leu Val Thr Val Ser Ser                 885 <210> 218 <211> 885 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro199 <400> 218 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             260 265 270 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser         275 280 285 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     290 295 300 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val 305 310 315 320 Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 325 330 335 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             340 345 350 Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         355 360 365 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu     370 375 380 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Thr Leu 385 390 395 400 Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn Leu Met                 405 410 415 Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val Ala Arg             420 425 430 Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys Gly Arg         435 440 445 Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met     450 455 460 Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn Leu Leu 465 470 475 480 Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln Gly Thr                 485 490 495 Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys             500 505 510 Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr         515 520 525 Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly     530 535 540 Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly 545 550 555 560 Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys                 565 570 575 Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala             580 585 590 Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys         595 600 605 Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu     610 615 620 Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val 625 630 635 640 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser                 645 650 655 Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val             660 665 670 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser         675 680 685 Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp     690 695 700 Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln 705 710 715 720 Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg                 725 730 735 His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly             740 745 750 Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly         755 760 765 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     770 775 780 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 785 790 795 800 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 805 810 815 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu             820 825 830 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr         835 840 845 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr     850 855 860 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu 865 870 875 880 Val Thr Val Ser Ser                 885 <210> 219 <211> 886 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro200 <400> 219 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser             20 25 30 Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu         35 40 45 Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser     50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr                 85 90 95 Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             260 265 270 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser         275 280 285 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     290 295 300 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val 305 310 315 320 Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 325 330 335 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             340 345 350 Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         355 360 365 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu     370 375 380 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Thr Leu 385 390 395 400 Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn Leu Met                 405 410 415 Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val Ala Arg             420 425 430 Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys Gly Arg         435 440 445 Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met     450 455 460 Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn Leu Leu 465 470 475 480 Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln Gly Thr                 485 490 495 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu             500 505 510 Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu         515 520 525 Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr     530 535 540 Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro 545 550 555 560 Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp                 565 570 575 Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala             580 585 590 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr         595 600 605 Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys     610 615 620 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu 625 630 635 640 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu                 645 650 655 Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp             660 665 670 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg         675 680 685 Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys     690 695 700 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu 705 710 715 720 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val                 725 730 735 Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp             740 745 750 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly         755 760 765 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln     770 775 780 Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 785 790 795 800 Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu                 805 810 815 Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala             820 825 830 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr         835 840 845 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val     850 855 860 Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr 865 870 875 880 Leu Val Thr Val Ser Ser                 885 <210> 220 <211> 903 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro189 (Pro186 with long linker between        inactivated aCD3 domains) <400> 220 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly 625 630 635 640 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly                 645 650 655 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser             660 665 670 Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro         675 680 685 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr     690 695 700 Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile 705 710 715 720 Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu                 725 730 735 Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe             740 745 750 Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu         755 760 765 Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val     770 775 780 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu 785 790 795 800 Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met                 805 810 815 Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser             820 825 830 Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly         835 840 845 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln     850 855 860 Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile 865 870 875 880 Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser                 885 890 895 Ser His His His His His His             900 <210> 221 <211> 636 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro206 (Pro186 active domain + aHSA) <400> 221 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly             500 505 510 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln         515 520 525 Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe     530 535 540 Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 545 550 555 560 Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala                 565 570 575 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr             580 585 590 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val         595 600 605 Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr     610 615 620 Leu Val Thr Val Ser Ser His His His His His His 625 630 635 <210> 222 <211> 513 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro227 (Pro22 aB7H3 hF7) <400> 222 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr             20 25 30 His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly         115 120 125 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu     130 135 140 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe 145 150 155 160 Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys                 165 170 175 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala             180 185 190 Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp         195 200 205 Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu     210 215 220 Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser 225 230 235 240 Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val                 245 250 255 Ser Ser Gly Gly Gly Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Gly             260 265 270 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro         275 280 285 Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr     290 295 300 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro 305 310 315 320 Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala                 325 330 335 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser             340 345 350 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr         355 360 365 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly     370 375 380 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly 385 390 395 400 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala                 405 410 415 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala             420 425 430 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg         435 440 445 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg     450 455 460 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro 465 470 475 480 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val                 485 490 495 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His             500 505 510 His      <210> 223 <211> 511 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro228 (Pro22 aB7H3 hF12) <400> 223 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr             20 25 30 Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val         35 40 45 Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly         115 120 125 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln     130 135 140 Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 145 150 155 160 Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu                 165 170 175 Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr             180 185 190 Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser         195 200 205 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr     210 215 220 Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile 225 230 235 240 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser                 245 250 255 Gly Gly Gly Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Gly Gly Ser             260 265 270 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly         275 280 285 Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly     290 295 300 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly 305 310 315 320 Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe                 325 330 335 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val             340 345 350 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn         355 360 365 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly     370 375 380 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly 385 390 395 400 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly                 405 410 415 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly             420 425 430 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr         435 440 445 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn     450 455 460 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp 465 470 475 480 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser                 485 490 495 Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His             500 505 510 <210> 224 <211> 512 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro244 (Pro51 aB7H3 hF7) <400> 224 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr             20 25 30 His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly         115 120 125 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu     130 135 140 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe 145 150 155 160 Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys                 165 170 175 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala             180 185 190 Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp         195 200 205 Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu     210 215 220 Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser 225 230 235 240 Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val                 245 250 255 Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly             260 265 270 Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly         275 280 285 Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser     290 295 300 Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg 305 310 315 320 Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg                 325 330 335 Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly             340 345 350 Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser         355 360 365 Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly     370 375 380 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly 385 390 395 400 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser                 405 410 415 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro             420 425 430 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp         435 440 445 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp     450 455 460 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu 465 470 475 480 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser                 485 490 495 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His             500 505 510 <210> 225 <211> 510 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro245 (Pro51 aB7H3 hF12) <400> 225 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr             20 25 30 Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val         35 40 45 Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly         115 120 125 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln     130 135 140 Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 145 150 155 160 Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu                 165 170 175 Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr             180 185 190 Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser         195 200 205 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr     210 215 220 Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile 225 230 235 240 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser                 245 250 255 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln             260 265 270 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr         275 280 285 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn     290 295 300 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu 305 310 315 320 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser                 325 330 335 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln             340 345 350 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg         355 360 365 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly     370 375 380 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 385 390 395 400 Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe                 405 410 415 Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys             420 425 430 Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu         435 440 445 Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala     450 455 460 Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr 465 470 475 480 Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln                 485 490 495 Gly Thr Leu Val Thr Val Ser Ser His His His His His His             500 505 510 <210> 226 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro247 (humanized Pro186 with Meprin        linker) <400> 226 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys             500 505 510 Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 227 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro248 (humanized Pro186 with CathS linker) <400> 227 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Ala Arg             500 505 510 Leu Gln Ser Ala Ala Pro Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 228 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro249 (humanized Pro186 with        Meprin / GranzymeB linker) <400> 228 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Val Tyr             500 505 510 Ala Asp Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 229 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro250 (humanized Pro186 with S9-        CathS / MMP9 linker) <400> 229 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ala Arg Leu Gln Ser             500 505 510 Ala Ala Pro Ala Gly Leu Lys Gly Ala Gly Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 230 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro251 (humanized Pro186 with ST14 (MS)        linker) <400> 230 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Leu Ser             500 505 510 Gly Arg Ser Asp Asn His Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 231 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro252 (humanized Pro186 with ST14 (MV)        linker) <400> 231 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Phe Thr             500 505 510 Arg Gln Ala Arg Val Val Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 232 <211> 897 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro253 (humanized Pro186 with MMP9v linker) <400> 232 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Gly Gly Pro Gly             500 505 510 Pro Ala Gly Met His Gly Leu Pro Gly Gly Ser Gln Thr Val Val Thr         515 520 525 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr     530 535 540 Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp 545 550 555 560 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr                 565 570 575 Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu             580 585 590 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp         595 600 605 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe     610 615 620 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly                 645 650 655 Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys             660 665 670 Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp         675 680 685 Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys     690 695 700 Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys 705 710 715 720 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala                 725 730 735 Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser             740 745 750 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly         755 760 765 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly     770 775 780 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala 785 790 795 800 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala                 805 810 815 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg             820 825 830 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg         835 840 845 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro     850 855 860 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val 865 870 875 880 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His                 885 890 895 His      <210> 233 <211> 902 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro261 (humanized Pro186 with a long active        domain aCD3 linker) <400> 233 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser             260 265 270 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly         275 280 285 Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly     290 295 300 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly 305 310 315 320 Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe                 325 330 335 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val             340 345 350 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn         355 360 365 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly     370 375 380 Ser Gly Gly Gly Ser Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val 385 390 395 400 Val Arg Pro Gly Gly Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg                 405 410 415 Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys             420 425 430 Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly         435 440 445 Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala     450 455 460 Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 465 470 475 480 Ala Leu Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr                 485 490 495 Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             500 505 510 Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser         515 520 525 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly     530 535 540 Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly 545 550 555 560 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly                 565 570 575 Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg             580 585 590 Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly         595 600 605 Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser     610 615 620 Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly                 645 650 655 Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly             660 665 670 Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly         675 680 685 Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys     690 695 700 Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser 705 710 715 720 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys                 725 730 735 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly             740 745 750 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val         755 760 765 Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln     770 775 780 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg 785 790 795 800 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser                 805 810 815 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile             820 825 830 Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg         835 840 845 Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met     850 855 860 Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly 865 870 875 880 Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 895 His His His His His His             900 <210> 234 <211> 901 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro294 (FL haEGFR2 MMP9 linker) <400> 234 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr             20 25 30 Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr             100 105 110 Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly         115 120 125 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     130 135 140 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser 145 150 155 160 Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro                 165 170 175 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn             180 185 190 Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser         195 200 205 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys     210 215 220 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly 225 230 235 240 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val                 245 250 255 Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val             260 265 270 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         275 280 285 Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     290 295 300 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly 305 310 315 320 Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 325 330 335 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             340 345 350 Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe         355 360 365 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly     370 375 380 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 385 390 395 400 Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser                 405 410 415 Tyr Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe             420 425 430 Val Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser         435 440 445 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu     450 455 460 Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr 465 470 475 480 Cys Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp                 485 490 495 Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser             500 505 510 Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln         515 520 525 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr     530 535 540 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn 545 550 555 560 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu                 565 570 575 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe             580 585 590 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val         595 600 605 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn     610 615 620 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp     690 695 700 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg 705 710 715 720 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr                 725 730 735 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn             740 745 750 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr         755 760 765 Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     770 775 780 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu 785 790 795 800 Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp                 805 810 815 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser             820 825 830 Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe         835 840 845 Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn     850 855 860 Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly 865 870 875 880 Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His                 885 890 895 His His His His His             900 <210> 235 <211> 895 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro295 (FL aB7H3 hF7 NC linker) <400> 235 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr             20 25 30 His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val             420 425 430 Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 465 470 475 480 Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly             500 505 510 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu 625 630 635 640 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser                 645 650 655 Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala             660 665 670 Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala         675 680 685 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp     690 695 700 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 705 710 715 720 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 725 730 735 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             740 745 750 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly         755 760 765 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly     770 775 780 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 785 790 795 800 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly                 805 810 815 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr             820 825 830 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         835 840 845 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp     850 855 860 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser 865 870 875 880 Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 236 <211> 891 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro296 (FL aB7H3 hF12 NC linker) <400> 236 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr             20 25 30 Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val         35 40 45 Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             260 265 270 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser         275 280 285 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     290 295 300 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val 305 310 315 320 Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 325 330 335 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             340 345 350 Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         355 360 365 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu     370 375 380 Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 385 390 395 400 Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr Ser Met Ala Trp                 405 410 415 Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val Ala Ala Ile Asn             420 425 430 Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe         435 440 445 Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn     450 455 460 Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Gly 465 470 475 480 Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr                 485 490 495 Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser             500 505 510 Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr         515 520 525 Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly     530 535 540 Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly 545 550 555 560 Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys                 565 570 575 Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala             580 585 590 Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys         595 600 605 Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu     610 615 620 Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val 625 630 635 640 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser                 645 650 655 Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val             660 665 670 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser         675 680 685 Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp     690 695 700 Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln 705 710 715 720 Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg                 725 730 735 His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly             740 745 750 Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly         755 760 765 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     770 775 780 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 785 790 795 800 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 805 810 815 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu             820 825 830 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr         835 840 845 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr     850 855 860 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu 865 870 875 880 Val Thr Val Ser Ser His His His His His His                 885 890 <210> 237 <211> 876 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro297 (FL aFOLR1 h77-2 KLK7.6 linker) <400> 237 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu         115 120 125 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys     130 135 140 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg 145 150 155 160 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys                 165 170 175 Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe             180 185 190 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         195 200 205 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala     210 215 220 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln                 245 250 255 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr             260 265 270 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn         275 280 285 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu     290 295 300 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser 305 310 315 320 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln                 325 330 335 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg             340 345 350 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser         355 360 365 Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     370 375 380 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 385 390 395 400 Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu                 405 410 415 Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala             420 425 430 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn         435 440 445 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val     450 455 460 Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr 465 470 475 480 Leu Val Thr Val Ser Ser Ser Gly Gly Gly Gln Asn Pro Tyr Ser Ala                 485 490 495 Gly Arg Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu             500 505 510 Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr         515 520 525 Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro     530 535 540 Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp 545 550 555 560 Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 565 570 575 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             580 585 590 Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         595 600 605 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     610 615 620 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu 625 630 635 640 Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp                 645 650 655 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg             660 665 670 Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys         675 680 685 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu     690 695 700 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val 705 710 715 720 Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp                 725 730 735 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly             740 745 750 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln         755 760 765 Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe     770 775 780 Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 785 790 795 800 Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala                 805 810 815 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr             820 825 830 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val         835 840 845 Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr     850 855 860 Leu Val Thr Val Ser Ser His His His His His His 865 870 875 <210> 238 <211> 876 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro298 (FL aFOLR1 h77-2 KLK7.11 linker) <400> 238 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu         115 120 125 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys     130 135 140 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg 145 150 155 160 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys                 165 170 175 Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe             180 185 190 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         195 200 205 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala     210 215 220 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln                 245 250 255 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr             260 265 270 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn         275 280 285 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu     290 295 300 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser 305 310 315 320 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln                 325 330 335 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg             340 345 350 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser         355 360 365 Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     370 375 380 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 385 390 395 400 Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu                 405 410 415 Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala             420 425 430 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn         435 440 445 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val     450 455 460 Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr 465 470 475 480 Leu Val Thr Val Ser Ser Ser Gly Gly Gly Arg Asn Val Tyr Ser Ala                 485 490 495 Gly Gly Gly Ser Gly Gly Gln Thr Val Val Thr Gln Glu Pro Ser Leu             500 505 510 Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr         515 520 525 Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro     530 535 540 Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp 545 550 555 560 Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 565 570 575 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             580 585 590 Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         595 600 605 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     610 615 620 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu 625 630 635 640 Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp                 645 650 655 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg             660 665 670 Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys         675 680 685 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu     690 695 700 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val 705 710 715 720 Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp                 725 730 735 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly             740 745 750 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln         755 760 765 Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe     770 775 780 Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 785 790 795 800 Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala                 805 810 815 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr             820 825 830 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val         835 840 845 Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr     850 855 860 Leu Val Thr Val Ser Ser His His His His His His 865 870 875 <210> 239 <211> 876 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro299 (FL aFOLR1 h77-2 NC linker) <400> 239 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu         115 120 125 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys     130 135 140 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg 145 150 155 160 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys                 165 170 175 Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe             180 185 190 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         195 200 205 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala     210 215 220 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln                 245 250 255 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr             260 265 270 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn         275 280 285 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu     290 295 300 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser 305 310 315 320 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln                 325 330 335 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg             340 345 350 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser         355 360 365 Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     370 375 380 Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 385 390 395 400 Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu                 405 410 415 Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala             420 425 430 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn         435 440 445 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val     450 455 460 Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr 465 470 475 480 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly                 485 490 495 Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu             500 505 510 Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr         515 520 525 Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro     530 535 540 Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp 545 550 555 560 Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 565 570 575 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             580 585 590 Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         595 600 605 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     610 615 620 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu 625 630 635 640 Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp                 645 650 655 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg             660 665 670 Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys         675 680 685 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu     690 695 700 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val 705 710 715 720 Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp                 725 730 735 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly             740 745 750 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln         755 760 765 Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe     770 775 780 Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 785 790 795 800 Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala                 805 810 815 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr             820 825 830 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val         835 840 845 Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr     850 855 860 Leu Val Thr Val Ser Ser His His His His His His 865 870 875 <210> 240 <211> 502 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro300 (Pro51 aFOLR1 h77-2) <400> 240 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val         115 120 125 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser     130 135 140 Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val 145 150 155 160 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser                 165 170 175 Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg             180 185 190 Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met         195 200 205 Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His     210 215 220 Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln 225 230 235 240 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly                 245 250 255 Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             260 265 270 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser         275 280 285 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     290 295 300 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val 305 310 315 320 Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 325 330 335 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             340 345 350 Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         355 360 365 Leu Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln     370 375 380 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg 385 390 395 400 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser                 405 410 415 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile             420 425 430 Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg         435 440 445 Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met     450 455 460 Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly 465 470 475 480 Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 485 490 495 His His His His His His             500 <210> 241 <211> 874 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro301 (FL aFOLR1 h59.3 KLK7.6 linker) <400> 241 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser             20 25 30 Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val         35 40 45 Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys                 85 90 95 His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             100 105 110 Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         115 120 125 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala     130 135 140 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr                 165 170 175 Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr             180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn         195 200 205 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn     210 215 220 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr                 245 250 255 Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val             260 265 270 Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr         275 280 285 Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile     290 295 300 Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly 305 310 315 320 Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro                 325 330 335 Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp             340 345 350 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly         355 360 365 Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln     370 375 380 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe 385 390 395 400 Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg                 405 410 415 Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp             420 425 430 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr         435 440 445 Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr     450 455 460 Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val 465 470 475 480 Thr Val Ser Ser Ser Gly Gly Gly Gln Asn Pro Tyr Ser Ala Gly Arg                 485 490 495 Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val             500 505 510 Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala         515 520 525 Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln     530 535 540 Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly 545 550 555 560 Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu                 565 570 575 Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val             580 585 590 Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr         595 600 605 Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu     610 615 620 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys 625 630 635 640 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg                 645 650 655 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys             660 665 670 Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg         675 680 685 Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met     690 695 700 Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 705 710 715 720 Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln                 725 730 735 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly             740 745 750 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly         755 760 765 Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys     770 775 780 Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 785 790 795 800 Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser                 805 810 815 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu             820 825 830 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr         835 840 845 Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val     850 855 860 Thr Val Ser Ser His His His His His His 865 870 <210> 242 <211> 874 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro302 (FL aFOLR1 h59.3 KLK7.11 linker) <400> 242 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser             20 25 30 Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val         35 40 45 Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys                 85 90 95 His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             100 105 110 Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         115 120 125 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala     130 135 140 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr                 165 170 175 Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr             180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn         195 200 205 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn     210 215 220 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr                 245 250 255 Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val             260 265 270 Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr         275 280 285 Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile     290 295 300 Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly 305 310 315 320 Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro                 325 330 335 Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp             340 345 350 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly         355 360 365 Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln     370 375 380 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe 385 390 395 400 Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg                 405 410 415 Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp             420 425 430 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr         435 440 445 Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr     450 455 460 Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val 465 470 475 480 Thr Val Ser Ser Ser Gly Gly Gly Arg Asn Val Tyr Ser Ala Gly Gly                 485 490 495 Gly Ser Gly Gly Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val             500 505 510 Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala         515 520 525 Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln     530 535 540 Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly 545 550 555 560 Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu                 565 570 575 Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val             580 585 590 Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr         595 600 605 Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu     610 615 620 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys 625 630 635 640 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg                 645 650 655 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys             660 665 670 Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg         675 680 685 Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met     690 695 700 Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 705 710 715 720 Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln                 725 730 735 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly             740 745 750 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly         755 760 765 Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys     770 775 780 Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 785 790 795 800 Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser                 805 810 815 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu             820 825 830 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr         835 840 845 Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val     850 855 860 Thr Val Ser Ser His His His His His His 865 870 <210> 243 <211> 874 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro303 (FL aFOLR1 h59.3 NC linker) <400> 243 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser             20 25 30 Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val         35 40 45 Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys                 85 90 95 His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             100 105 110 Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         115 120 125 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala     130 135 140 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr                 165 170 175 Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr             180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn         195 200 205 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn     210 215 220 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr                 245 250 255 Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val             260 265 270 Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr         275 280 285 Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile     290 295 300 Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly 305 310 315 320 Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro                 325 330 335 Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp             340 345 350 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly         355 360 365 Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln     370 375 380 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe 385 390 395 400 Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg                 405 410 415 Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp             420 425 430 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr         435 440 445 Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr     450 455 460 Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val 465 470 475 480 Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser                 485 490 495 Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val             500 505 510 Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala         515 520 525 Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln     530 535 540 Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly 545 550 555 560 Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu                 565 570 575 Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val             580 585 590 Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr         595 600 605 Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu     610 615 620 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys 625 630 635 640 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg                 645 650 655 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys             660 665 670 Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg         675 680 685 Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met     690 695 700 Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 705 710 715 720 Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln                 725 730 735 Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly             740 745 750 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly         755 760 765 Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys     770 775 780 Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 785 790 795 800 Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser                 805 810 815 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu             820 825 830 Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr         835 840 845 Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val     850 855 860 Thr Val Ser Ser His His His His His His 865 870 <210> 244 <211> 501 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro304 (Pro51 aFOLR1 h59.3) <400> 244 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser             20 25 30 Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val         35 40 45 Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys                 85 90 95 His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             100 105 110 Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu         115 120 125 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys     130 135 140 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg 145 150 155 160 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys                 165 170 175 Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe             180 185 190 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         195 200 205 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala     210 215 220 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly                 245 250 255 Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu             260 265 270 Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr         275 280 285 Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro     290 295 300 Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro 305 310 315 320 Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala                 325 330 335 Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys             340 345 350 Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu         355 360 365 Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     370 375 380 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu 385 390 395 400 Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp                 405 410 415 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser             420 425 430 Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe         435 440 445 Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn     450 455 460 Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly 465 470 475 480 Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His                 485 490 495 His His His His His             500 <210> 245 <211> 882 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro305 (FL aFOLR1 h22.4 KLK7.6 linker) <400> 245 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln         115 120 125 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys     130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile                 165 170 175 Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys             180 185 190 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu         195 200 205 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val     210 215 220 Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp 225 230 235 240 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly                 245 250 255 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro             260 265 270 Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr         275 280 285 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro     290 295 300 Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala 305 310 315 320 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser                 325 330 335 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr             340 345 350 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser 385 390 395 400 Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val 465 470 475 480 Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Gly                 485 490 495 Arg Asn Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val             500 505 510 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         515 520 525 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     530 535 540 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp 545 550 555 560 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser                 565 570 575 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu             580 585 590 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val         595 600 605 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly     610 615 620 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro 625 630 635 640 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn                 645 650 655 Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu             660 665 670 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp         675 680 685 Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser     690 695 700 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr 705 710 715 720 Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile                 725 730 735 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser             740 745 750 Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         755 760 765 Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala     770 775 780 Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln 785 790 795 800 Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly                 805 810 815 Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser             820 825 830 Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg         835 840 845 Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser     850 855 860 Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His 865 870 875 880 His His          <210> 246 <211> 882 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro306 (FL aFOLR1 h22.4 KLK7.11 linker) <400> 246 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln         115 120 125 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys     130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile                 165 170 175 Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys             180 185 190 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu         195 200 205 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val     210 215 220 Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp 225 230 235 240 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly                 245 250 255 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro             260 265 270 Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr         275 280 285 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro     290 295 300 Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala 305 310 315 320 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser                 325 330 335 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr             340 345 350 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser 385 390 395 400 Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val 465 470 475 480 Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Gly                 485 490 495 Arg Asn Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val             500 505 510 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         515 520 525 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     530 535 540 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp 545 550 555 560 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser                 565 570 575 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu             580 585 590 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val         595 600 605 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly     610 615 620 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro 625 630 635 640 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn                 645 650 655 Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu             660 665 670 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp         675 680 685 Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser     690 695 700 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr 705 710 715 720 Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile                 725 730 735 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser             740 745 750 Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         755 760 765 Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala     770 775 780 Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln 785 790 795 800 Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly                 805 810 815 Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser             820 825 830 Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg         835 840 845 Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser     850 855 860 Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His 865 870 875 880 His His          <210> 247 <211> 882 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro307 (FL aFOLR1 h22.4 NC linker) <400> 247 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln         115 120 125 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys     130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile                 165 170 175 Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys             180 185 190 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu         195 200 205 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val     210 215 220 Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp 225 230 235 240 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly                 245 250 255 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro             260 265 270 Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr         275 280 285 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro     290 295 300 Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala 305 310 315 320 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser                 325 330 335 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr             340 345 350 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser 385 390 395 400 Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val 465 470 475 480 Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser                 485 490 495 Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val             500 505 510 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         515 520 525 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     530 535 540 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp 545 550 555 560 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser                 565 570 575 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu             580 585 590 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val         595 600 605 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly     610 615 620 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro 625 630 635 640 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn                 645 650 655 Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu             660 665 670 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp         675 680 685 Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser     690 695 700 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr 705 710 715 720 Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile                 725 730 735 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser             740 745 750 Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         755 760 765 Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala     770 775 780 Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln 785 790 795 800 Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly                 805 810 815 Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser             820 825 830 Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg         835 840 845 Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser     850 855 860 Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His 865 870 875 880 His His          <210> 248 <211> 505 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro308 (Pro51 aFOLR1 h22.4) <400> 248 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val         115 120 125 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu     130 135 140 Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile 145 150 155 160 Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg                 165 170 175 Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val             180 185 190 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr         195 200 205 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys     210 215 220 Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr 225 230 235 240 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser                 245 250 255 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln             260 265 270 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys         275 280 285 Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val     290 295 300 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys 305 310 315 320 Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly                 325 330 335 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala             340 345 350 Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly         355 360 365 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Ser     370 375 380 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn 385 390 395 400 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe                 405 410 415 Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val             420 425 430 Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val         435 440 445 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr     450 455 460 Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys 465 470 475 480 Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr                 485 490 495 Val Ser Ser His His His His His His             500 505 <210> 249 <211> 901 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro335 (FL aEGFR2 NC linker) <400> 249 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr             20 25 30 Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr             100 105 110 Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly         115 120 125 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     130 135 140 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser 145 150 155 160 Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro                 165 170 175 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn             180 185 190 Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser         195 200 205 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys     210 215 220 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly 225 230 235 240 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val                 245 250 255 Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val             260 265 270 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         275 280 285 Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     290 295 300 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly 305 310 315 320 Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 325 330 335 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             340 345 350 Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe         355 360 365 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly     370 375 380 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 385 390 395 400 Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser                 405 410 415 Tyr Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe             420 425 430 Val Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser         435 440 445 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu     450 455 460 Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr 465 470 475 480 Cys Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp                 485 490 495 Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser             500 505 510 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln         515 520 525 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr     530 535 540 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn 545 550 555 560 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu                 565 570 575 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe             580 585 590 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val         595 600 605 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn     610 615 620 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp     690 695 700 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg 705 710 715 720 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr                 725 730 735 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn             740 745 750 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr         755 760 765 Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     770 775 780 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu 785 790 795 800 Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp                 805 810 815 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser             820 825 830 Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe         835 840 845 Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn     850 855 860 Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly 865 870 875 880 Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His                 885 890 895 His His His His His             900 <210> 250 <211> 894 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro345 (humanized Pro186 Vli2 domain MMP9        linker) <400> 250 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro             500 505 510 Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp                 565 570 575 Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val 625 630 635 640 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu                 645 650 655 Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met             660 665 670 Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg         675 680 685 Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser     690 695 700 Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala 705 710 715 720 Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr                 725 730 735 Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala             740 745 750 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly         755 760 765 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu     770 775 780 Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 785 790 795 800 Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys                 805 810 815 Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu             820 825 830 Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala         835 840 845 Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr     850 855 860 Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln 865 870 875 880 Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 <210> 251 <211> 894 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro346 (humanized Pro186 Vli2 domain NC        linker) <400> 251 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu 385 390 395 400 Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly             500 505 510 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp                 565 570 575 Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly             580 585 590 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu         595 600 605 Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly     610 615 620 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val 625 630 635 640 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu                 645 650 655 Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met             660 665 670 Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg         675 680 685 Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser     690 695 700 Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala 705 710 715 720 Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr                 725 730 735 Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala             740 745 750 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly         755 760 765 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu     770 775 780 Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 785 790 795 800 Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys                 805 810 815 Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu             820 825 830 Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala         835 840 845 Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr     850 855 860 Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln 865 870 875 880 Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 <210> 252 <211> 880 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro368 (FL aFOLR1 wt22.4 MMP9 linker) <400> 252 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln         115 120 125 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys     130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile                 165 170 175 Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys             180 185 190 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu         195 200 205 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val     210 215 220 Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp 225 230 235 240 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly                 245 250 255 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro             260 265 270 Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr         275 280 285 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro     290 295 300 Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala 305 310 315 320 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser                 325 330 335 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr             340 345 350 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser 385 390 395 400 Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Ala Pro Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val 465 470 475 480 Phe Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro                 485 490 495 Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr             500 505 510 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr         515 520 525 Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp     530 535 540 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr 545 550 555 560 Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu                 565 570 575 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu             580 585 590 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly         595 600 605 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser     610 615 620 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 625 630 635 640 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr                 645 650 655 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val             660 665 670 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala         675 680 685 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn     690 695 700 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 705 710 715 720 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr                 725 730 735 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly             740 745 750 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly         755 760 765 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser     770 775 780 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro 785 790 795 800 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp                 805 810 815 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp             820 825 830 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu         835 840 845 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser     850 855 860 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His 865 870 875 880 <210> 253 <211> 881 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro369 (FL aFOLR1 wt22.4 KLK7.6 linker) <400> 253 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln         115 120 125 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys     130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile                 165 170 175 Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys             180 185 190 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu         195 200 205 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val     210 215 220 Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp 225 230 235 240 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly                 245 250 255 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro             260 265 270 Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr         275 280 285 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro     290 295 300 Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala 305 310 315 320 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser                 325 330 335 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr             340 345 350 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser 385 390 395 400 Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Ala Pro Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val 465 470 475 480 Phe Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly                 485 490 495 Gln Asn Pro Tyr Ser Ala Gly Arg Gly Gly Gly Ser Gln Thr Val Val             500 505 510 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         515 520 525 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     530 535 540 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly 545 550 555 560 Thr Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 565 570 575 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             580 585 590 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe         595 600 605 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly     610 615 620 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 625 630 635 640 Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys                 645 650 655 Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp             660 665 670 Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys         675 680 685 Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys     690 695 700 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala 705 710 715 720 Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser                 725 730 735 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly             740 745 750 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly         755 760 765 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala     770 775 780 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala 785 790 795 800 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg                 805 810 815 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg             820 825 830 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro         835 840 845 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val     850 855 860 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His 865 870 875 880 His      <210> 254 <211> 881 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro370 (FL aFOLR1 wt22.4 KLK7.11 linker) <400> 254 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln         115 120 125 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys     130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile                 165 170 175 Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys             180 185 190 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu         195 200 205 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val     210 215 220 Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp 225 230 235 240 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly                 245 250 255 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro             260 265 270 Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr         275 280 285 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro     290 295 300 Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala 305 310 315 320 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser                 325 330 335 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr             340 345 350 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser 385 390 395 400 Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Ala Pro Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val 465 470 475 480 Phe Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly                 485 490 495 Arg Asn Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val             500 505 510 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         515 520 525 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     530 535 540 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly 545 550 555 560 Thr Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 565 570 575 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             580 585 590 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe         595 600 605 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly     610 615 620 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 625 630 635 640 Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys                 645 650 655 Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp             660 665 670 Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys         675 680 685 Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys     690 695 700 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala 705 710 715 720 Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser                 725 730 735 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly             740 745 750 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly         755 760 765 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala     770 775 780 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala 785 790 795 800 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg                 805 810 815 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg             820 825 830 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro         835 840 845 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val     850 855 860 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His 865 870 875 880 His      <210> 255 <211> 881 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro371 (FL aFOLR1 wt22.4 NC linker) <400> 255 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln         115 120 125 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys     130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile                 165 170 175 Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys             180 185 190 Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu         195 200 205 Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val     210 215 220 Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp 225 230 235 240 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly                 245 250 255 Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro             260 265 270 Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr         275 280 285 Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro     290 295 300 Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala 305 310 315 320 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser                 325 330 335 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr             340 345 350 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser 385 390 395 400 Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Ala Pro Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val 465 470 475 480 Phe Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser                 485 490 495 Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val             500 505 510 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu         515 520 525 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn     530 535 540 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly 545 550 555 560 Thr Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 565 570 575 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             580 585 590 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe         595 600 605 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly     610 615 620 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 625 630 635 640 Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys                 645 650 655 Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp             660 665 670 Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys         675 680 685 Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys     690 695 700 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala 705 710 715 720 Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser                 725 730 735 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly             740 745 750 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly         755 760 765 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala     770 775 780 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala 785 790 795 800 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg                 805 810 815 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg             820 825 830 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro         835 840 845 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val     850 855 860 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His 865 870 875 880 His      <210> 256 <211> 505 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro372 (Pro51 aFOLR1 wt22.4) <400> 256 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp             20 25 30 Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val         35 40 45 Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn                 85 90 95 Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln             100 105 110 Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val         115 120 125 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu     130 135 140 Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile 145 150 155 160 Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg                 165 170 175 Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val             180 185 190 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr         195 200 205 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys     210 215 220 Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr 225 230 235 240 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser                 245 250 255 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln             260 265 270 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys         275 280 285 Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val     290 295 300 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys 305 310 315 320 Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly                 325 330 335 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala             340 345 350 Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly         355 360 365 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Ser     370 375 380 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn 385 390 395 400 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe                 405 410 415 Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val             420 425 430 Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val         435 440 445 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr     450 455 460 Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys 465 470 475 480 Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr                 485 490 495 Val Ser Ser His His His His His His             500 505 <210> 257 <211> 895 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro373 (FL aB7H3 hF7 Meprin linker) <400> 257 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr             20 25 30 His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val             420 425 430 Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 465 470 475 480 Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Gly Lys Lys             500 505 510 Leu Ala Asp Glu Pro Glu Gly Gly Ser Gln Thr Val Val Thr Gln Glu         515 520 525 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly     530 535 540 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln 545 550 555 560 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp                 565 570 575 Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly             580 585 590 Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala         595 600 605 Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly     610 615 620 Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu 625 630 635 640 Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser                 645 650 655 Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala             660 665 670 Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala         675 680 685 Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp     690 695 700 Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 705 710 715 720 Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr                 725 730 735 Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp             740 745 750 Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly         755 760 765 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly     770 775 780 Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 785 790 795 800 Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly                 805 810 815 Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr             820 825 830 Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         835 840 845 Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp     850 855 860 Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser 865 870 875 880 Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895 <210> 258 <211> 891 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro374 (FL aB7H3 hF12 Meprin linker) <400> 258 Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr             20 25 30 Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val         35 40 45 Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys                 85 90 95 Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp             100 105 110 Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly         115 120 125 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     130 135 140 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn 145 150 155 160 Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 165 170 175 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr             180 185 190 Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys         195 200 205 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala     210 215 220 Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser 225 230 235 240 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly                 245 250 255 Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             260 265 270 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser         275 280 285 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     290 295 300 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val 305 310 315 320 Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala                 325 330 335 Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr             340 345 350 Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys         355 360 365 Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu     370 375 380 Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 385 390 395 400 Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr Ser Met Ala Trp                 405 410 415 Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val Ala Ala Ile Asn             420 425 430 Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe         435 440 445 Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn     450 455 460 Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Gly 465 470 475 480 Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr                 485 490 495 Leu Val Thr Val Ser Ser Ser Gly Gly Gly Lys Lys Leu Ala Asp Glu             500 505 510 Pro Glu Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr         515 520 525 Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly     530 535 540 Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly 545 550 555 560 Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys                 565 570 575 Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala             580 585 590 Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys         595 600 605 Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu     610 615 620 Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val 625 630 635 640 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser                 645 650 655 Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val             660 665 670 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser         675 680 685 Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp     690 695 700 Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln 705 710 715 720 Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg                 725 730 735 His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly             740 745 750 Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly         755 760 765 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     770 775 780 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 785 790 795 800 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 805 810 815 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu             820 825 830 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr         835 840 845 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr     850 855 860 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu 865 870 875 880 Val Thr Val Ser Ser His His His His His His                 885 890 <210> 259 <211> 898 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro375 (FL hEGFR1 / hEGFR2 Meprin linker) <400> 259 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr Ala Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Val Ala             420 425 430 Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln     450 455 460 Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 465 470 475 480 Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr Glu Tyr                 485 490 495 Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly             500 505 510 Gly Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Ser Gln Thr Val Val         515 520 525 Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu     530 535 540 Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn 545 550 555 560 Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp                 565 570 575 Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser             580 585 590 Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu         595 600 605 Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val     610 615 620 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly 625 630 635 640 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro                 645 650 655 Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn             660 665 670 Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu         675 680 685 Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp     690 695 700 Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser 705 710 715 720 Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr                 725 730 735 Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile             740 745 750 Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser         755 760 765 Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser     770 775 780 Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala 785 790 795 800 Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln                 805 810 815 Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly             820 825 830 Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser         835 840 845 Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg     850 855 860 Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser 865 870 875 880 Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His                 885 890 895 His His          <210> 260 <211> 902 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro376 (Pro262 Meprin linker) <400> 260 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser             260 265 270 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly         275 280 285 Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly     290 295 300 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly 305 310 315 320 Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe                 325 330 335 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val             340 345 350 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn         355 360 365 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly     370 375 380 Ser Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser 385 390 395 400 Val Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg                 405 410 415 Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys             420 425 430 Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly         435 440 445 Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala     450 455 460 Lys Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr 465 470 475 480 Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr                 485 490 495 Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser             500 505 510 Ser Ser Gly Gly Gly Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Ser         515 520 525 Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly     530 535 540 Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly 545 550 555 560 Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly                 565 570 575 Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg             580 585 590 Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly         595 600 605 Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser     610 615 620 Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly 625 630 635 640 Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly                 645 650 655 Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly             660 665 670 Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly         675 680 685 Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys     690 695 700 Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser 705 710 715 720 Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys                 725 730 735 Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly             740 745 750 Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val         755 760 765 Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln     770 775 780 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg 785 790 795 800 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser                 805 810 815 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile             820 825 830 Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg         835 840 845 Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met     850 855 860 Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly 865 870 875 880 Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser                 885 890 895 His His His His His His             900 <210> 261 <211> 877 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro390 (FL aFOLR1 h59.3 extended central        linker MMP9 linker) <400> 261 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser             20 25 30 Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val         35 40 45 Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys                 85 90 95 His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             100 105 110 Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         115 120 125 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala     130 135 140 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr                 165 170 175 Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr             180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn         195 200 205 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn     210 215 220 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr                 245 250 255 Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val             260 265 270 Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr         275 280 285 Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile     290 295 300 Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly 305 310 315 320 Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro                 325 330 335 Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp             340 345 350 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro 385 390 395 400 Gly Asn Thr Phe Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln 465 470 475 480 Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly                 485 490 495 Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser             500 505 510 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser         515 520 525 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys     530 535 540 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp 545 550 555 560 Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys                 565 570 575 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr             580 585 590 Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr         595 600 605 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln     610 615 620 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys 625 630 635 640 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn                 645 650 655 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile             660 665 670 Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val         675 680 685 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr     690 695 700 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys 705 710 715 720 Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr                 725 730 735 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser             740 745 750 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val         755 760 765 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr     770 775 780 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly 785 790 795 800 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr                 805 810 815 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys             820 825 830 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala         835 840 845 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly     850 855 860 Thr Leu Val Thr Val Ser Ser His His His His His His 865 870 875 <210> 262 <211> 881 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro391 (FL aFOLR1 h59.3 extended central        linker and extended MMP9 linker) <400> 262 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser             20 25 30 Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val         35 40 45 Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys                 85 90 95 His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser             100 105 110 Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser         115 120 125 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala     130 135 140 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr                 165 170 175 Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr             180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn         195 200 205 Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn     210 215 220 Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr                 245 250 255 Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val             260 265 270 Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr         275 280 285 Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile     290 295 300 Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly 305 310 315 320 Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro                 325 330 335 Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp             340 345 350 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly         355 360 365 Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly     370 375 380 Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro 385 390 395 400 Gly Asn Thr Phe Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro                 405 410 415 Gly Lys Gln Arg Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr             420 425 430 Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn         435 440 445 Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp     450 455 460 Thr Ala Val Tyr Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln 465 470 475 480 Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly                 485 490 495 Met Lys Gly Leu Pro Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr             500 505 510 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr         515 520 525 Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp     530 535 540 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr 545 550 555 560 Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu                 565 570 575 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp             580 585 590 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe         595 600 605 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly     610 615 620 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 625 630 635 640 Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys                 645 650 655 Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp             660 665 670 Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys         675 680 685 Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys     690 695 700 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala 705 710 715 720 Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser                 725 730 735 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly             740 745 750 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly         755 760 765 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala     770 775 780 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala 785 790 795 800 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg                 805 810 815 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg             820 825 830 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro         835 840 845 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val     850 855 860 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His 865 870 875 880 His      <210> 263 <211> 897 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro412 (Pro186 with 2aa extended central        linkers) <400> 263 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln     370 375 380 Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser 385 390 395 400 Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly                 405 410 415 Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser             420 425 430 Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys         435 440 445 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu     450 455 460 Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala 465 470 475 480 Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr                 485 490 495 Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Ser Gly Gly Pro             500 505 510 Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr         515 520 525 Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr     530 535 540 Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp 545 550 555 560 Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr                 565 570 575 Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu             580 585 590 Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp         595 600 605 Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe     610 615 620 Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly 625 630 635 640 Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly                 645 650 655 Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys             660 665 670 Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp         675 680 685 Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys     690 695 700 Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys 705 710 715 720 Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala                 725 730 735 Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser             740 745 750 Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly         755 760 765 Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly     770 775 780 Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala 785 790 795 800 Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala                 805 810 815 Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg             820 825 830 Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg         835 840 845 Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro     850 855 860 Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val 865 870 875 880 Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His                 885 890 895 His      <210> 264 <211> 899 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro413 (Pro186 with 4aa extended central        linkers) <400> 264 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser     370 375 380 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 385 390 395 400 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr                 405 410 415 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val             420 425 430 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val         435 440 445 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp     450 455 460 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys 465 470 475 480 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp                 485 490 495 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Ser Gly             500 505 510 Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val         515 520 525 Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr     530 535 540 Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro 545 550 555 560 Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly                 565 570 575 Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly             580 585 590 Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro         595 600 605 Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp     610 615 620 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly 625 630 635 640 Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln                 645 650 655 Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe             660 665 670 Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu         675 680 685 Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp     690 695 700 Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp 705 710 715 720 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp                 725 730 735 Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr             740 745 750 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser         755 760 765 Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu     770 775 780 Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys 785 790 795 800 Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg                 805 810 815 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser             820 825 830 Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile         835 840 845 Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu     850 855 860 Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu 865 870 875 880 Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His                 885 890 895 His His His              <210> 265 <211> 901 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro414 (Pro186 with 6aa extended central        linkers) <400> 265 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly     370 375 380 Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly 385 390 395 400 Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser                 405 410 415 Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe             420 425 430 Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser         435 440 445 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val     450 455 460 Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr 465 470 475 480 Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr                 485 490 495 Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly             500 505 510 Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln         515 520 525 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr     530 535 540 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn 545 550 555 560 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu                 565 570 575 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe             580 585 590 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val         595 600 605 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn     610 615 620 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly 625 630 635 640 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu                 645 650 655 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe             660 665 670 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys         675 680 685 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp     690 695 700 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg 705 710 715 720 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr                 725 730 735 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn             740 745 750 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr         755 760 765 Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu     770 775 780 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu 785 790 795 800 Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp                 805 810 815 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser             820 825 830 Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe         835 840 845 Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn     850 855 860 Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly 865 870 875 880 Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His                 885 890 895 His His His His His             900 <210> 266 <211> 903 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro415 (Pro186 with 8aa extended central        linkers) <400> 266 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly     370 375 380 Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr 385 390 395 400 Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg                 405 410 415 Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu             420 425 430 Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp         435 440 445 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr     450 455 460 Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr 465 470 475 480 Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu                 485 490 495 Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly             500 505 510 Gly Gly Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly         515 520 525 Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly     530 535 540 Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser 545 550 555 560 Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg                 565 570 575 Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala             580 585 590 Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser         595 600 605 Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr     610 615 620 Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 625 630 635 640 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly                 645 650 655 Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser             660 665 670 Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro         675 680 685 Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr     690 695 700 Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile 705 710 715 720 Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu                 725 730 735 Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe             740 745 750 Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu         755 760 765 Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val     770 775 780 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu 785 790 795 800 Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met                 805 810 815 Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser             820 825 830 Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly         835 840 845 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln     850 855 860 Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile 865 870 875 880 Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser                 885 890 895 Ser His His His His His His             900 <210> 267 <211> 893 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro416 (Pro186 with 2aa shortened central        linkers) <400> 267 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Ser Gly Gly Gly Ser Gln Val Lys     370 375 380 Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu Arg 385 390 395 400 Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly                 405 410 415 Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile             420 425 430 Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg         435 440 445 Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln Met     450 455 460 Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala Ala 465 470 475 480 Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly                 485 490 495 Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Pro Gly Pro Ala Gly             500 505 510 Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser         515 520 525 Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser     530 535 540 Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys 545 550 555 560 Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp                 565 570 575 Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys             580 585 590 Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr         595 600 605 Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr     610 615 620 Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln 625 630 635 640 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys                 645 650 655 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn             660 665 670 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile         675 680 685 Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val     690 695 700 Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr 705 710 715 720 Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys                 725 730 735 Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr             740 745 750 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser         755 760 765 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     770 775 780 Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 785 790 795 800 Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly                 805 810 815 Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr             820 825 830 Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys         835 840 845 Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala     850 855 860 Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly 865 870 875 880 Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 <210> 268 <211> 891 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro417 (Pro186 with 4aa shortened central        linkers) <400> 268 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Ser Gly Gly Gly Ser Gln Val Lys Leu     370 375 380 Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu Arg Leu 385 390 395 400 Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp                 405 410 415 Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser             420 425 430 Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe         435 440 445 Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln Met Asn     450 455 460 Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala Ala Ala 465 470 475 480 Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln                 485 490 495 Gly Thr Gln Val Thr Val Ser Ser Ser Gly Pro Gly Pro Ala Gly Met             500 505 510 Lys Gly Leu Pro Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr         515 520 525 Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly     530 535 540 Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly 545 550 555 560 Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys                 565 570 575 Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala             580 585 590 Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys         595 600 605 Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu     610 615 620 Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val 625 630 635 640 Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser                 645 650 655 Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val             660 665 670 Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser         675 680 685 Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp     690 695 700 Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln 705 710 715 720 Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg                 725 730 735 His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly             740 745 750 Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly         755 760 765 Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro     770 775 780 Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 785 790 795 800 Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu                 805 810 815 Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu             820 825 830 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr         835 840 845 Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr     850 855 860 Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu 865 870 875 880 Val Thr Val Ser Ser His His His His His His                 885 890 <210> 269 <211> 889 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro418 (Pro186 with 6aa shortened central        linkers) <400> 269 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gln Val Lys Leu Glu     370 375 380 Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu Arg Leu Thr 385 390 395 400 Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe                 405 410 415 Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp             420 425 430 Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr         435 440 445 Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln Met Asn Ser     450 455 460 Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly 465 470 475 480 Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly                 485 490 495 Thr Gln Val Thr Val Ser Ser Gly Pro Gly Pro Ala Gly Met Lys Gly             500 505 510 Leu Pro Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser         515 520 525 Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val     530 535 540 Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala 545 550 555 560 Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr                 565 570 575 Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr             580 585 590 Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu         595 600 605 Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val     610 615 620 Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser 625 630 635 640 Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala                 645 650 655 Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln             660 665 670 Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr         675 680 685 Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe     690 695 700 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn 705 710 715 720 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly                 725 730 735 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly             740 745 750 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser         755 760 765 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn     770 775 780 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe 785 790 795 800 Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val                 805 810 815 Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val             820 825 830 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr         835 840 845 Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys     850 855 860 Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr 865 870 875 880 Val Ser Ser His His His His His His                 885 <210> 270 <211> 885 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro420 (FL aFOLR1 h77.2 / haEGFR1        heterologous COBRA MMP9 linker) <400> 270 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser             20 25 30 Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val         35 40 45 Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys     50 55 60 Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 75 80 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn                 85 90 95 Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val             100 105 110 Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu         115 120 125 Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys     130 135 140 Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg 145 150 155 160 Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys                 165 170 175 Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe             180 185 190 Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn         195 200 205 Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala     210 215 220 Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly 225 230 235 240 Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln                 245 250 255 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr             260 265 270 Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn         275 280 285 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu     290 295 300 Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser 305 310 315 320 Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln                 325 330 335 Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg             340 345 350 Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser         355 360 365 Gly Gly Gly Ser Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val     370 375 380 Arg Pro Gly Gly Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr 385 390 395 400 Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu                 405 410 415 Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr             420 425 430 Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys         435 440 445 Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala     450 455 460 Leu Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu 465 470 475 480 Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser                 485 490 495 Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln             500 505 510 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr         515 520 525 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn     530 535 540 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu 545 550 555 560 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe                 565 570 575 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val             580 585 590 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn         595 600 605 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly     610 615 620 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 625 630 635 640 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe                 645 650 655 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys             660 665 670 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp         675 680 685 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg     690 695 700 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr 705 710 715 720 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn                 725 730 735 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr             740 745 750 Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu         755 760 765 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu     770 775 780 Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp 785 790 795 800 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser                 805 810 815 Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe             820 825 830 Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn         835 840 845 Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly     850 855 860 Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His 865 870 875 880 His His His His His                 885 <210> 271 <211> 885 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro421 (FL haEGFR1 / aFOLR1 h77.2        heterologous COBRA MMP9 linker) <400> 271 Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly 1 5 10 15 Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 385 390 395 400 Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser Val Met                 405 410 415 Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val Ala Ile             420 425 430 Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys Gly Arg         435 440 445 Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met     450 455 460 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn Arg Asn 465 470 475 480 Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser                 485 490 495 Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln             500 505 510 Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr         515 520 525 Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn     530 535 540 Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu 545 550 555 560 Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe                 565 570 575 Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val             580 585 590 Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn         595 600 605 Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly     610 615 620 Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 625 630 635 640 Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe                 645 650 655 Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys             660 665 670 Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp         675 680 685 Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg     690 695 700 Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr 705 710 715 720 Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn                 725 730 735 Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr             740 745 750 Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu         755 760 765 Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu     770 775 780 Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp 785 790 795 800 Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser                 805 810 815 Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe             820 825 830 Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn         835 840 845 Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly     850 855 860 Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His 865 870 875 880 His His His His His                 885 <210> 272 <211> 896 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct-Pro429 (Pro186 Meprin / GranzymeB linker) <400> 272 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr             20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val         35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val     50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys                 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser         115 120 125 Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val     130 135 140 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr 145 150 155 160 Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly                 165 170 175 Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr             180 185 190 Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp         195 200 205 Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp     210 215 220 Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr 225 230 235 240 Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser                 245 250 255 Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu             260 265 270 Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala         275 280 285 Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln     290 295 300 Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe 305 310 315 320 Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly                 325 330 335 Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu             340 345 350 Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly         355 360 365 Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val     370 375 380 Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu 385 390 395 400 Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met                 405 410 415 Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly             420 425 430 Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly         435 440 445 Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln     450 455 460 Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala 465 470 475 480 Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp                 485 490 495 Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Val Tyr             500 505 510 Ala Asp Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln         515 520 525 Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys     530 535 540 Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val 545 550 555 560 Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys                 565 570 575 Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu             580 585 590 Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu         595 600 605 Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly     610 615 620 Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser 625 630 635 640 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly                 645 650 655 Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr             660 665 670 Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val         675 680 685 Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala     690 695 700 Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 705 710 715 720 Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val                 725 730 735 Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr             740 745 750 Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly         755 760 765 Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly     770 775 780 Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser 785 790 795 800 Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro                 805 810 815 Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp             820 825 830 Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp         835 840 845 Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu     850 855 860 Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser 865 870 875 880 Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His                 885 890 895

Claims (49)

From N-terminus to C-terminus, for proteins comprising:
a) the first single domain antigen binding domain (sdABD) (sdABD-TTA) that binds to the human tumor target antigen (TTA);
b) the first domain linker;
c) Constrained Fv domain comprising:
i) the first variable heavy chain domain comprising vhCDR1, vhCDR2 and vhCDR3;
ii) Constrained Uncleavable Linker (CNCL); And
iii) the first variable light domain comprising vlCDR1, vlCDR2 and vlCDR3;
d) a second domain linker;
e) a second sdABD-TTA;
f) a cleavable linker (CL);
g) Constrained caustic Fv domains comprising:
i) the first pseudo light chain variable domain;
ii) non-cleavable linker (NCL); And
iii) the first pseudo heavy chain variable domain;
h) a third domain linker; And
i) a third sdABD that binds human serum albumin;
Wherein the first variable heavy chain domain and the first variable light chain domain can bind human CD3, but the restricted Fv domain does not bind CD3; Wherein the first variable heavy chain domain and the first pseudo variable light chain domain are intramolecularly linked to form an inactive Fv; And wherein the first variable light chain domain and the first pseudo variable heavy chain domain are intramolecularly linked to form an inactive Fv. From N-terminus to C-terminus, for proteins comprising:
a) the first sdABD-TTA;
b) the first domain linker;
c) Constrained Fv domain comprising:
i) the first variable heavy chain domain comprising vhCDR1, vhCDR2 and vhCDR3;
ii) constrained cleavable linker (CCL); And
iii) the first variable light domain comprising vlCDR1, vlCDR2 and vlCDR3;
d) a second domain linker;
e) a second sdABD-TTA;
f) a cleavable linker (CL);
g) Constrained caustic Fv domains comprising:
i) the first pseudo heavy chain variable domain;
ii) non-cleavable linker (NCL); And
iii) first pseudo light chain variable domain;
h) a third domain linker; And
i) a third sdABD that binds human serum albumin;
Wherein the first variable heavy chain domain and the first variable light chain domain can bind human CD3, but the restricted Fv domain does not bind CD3; Wherein the first variable heavy chain domain and the first pseudo variable light chain domain are intramolecularly linked to form an inactive Fv; And wherein the first variable light chain domain and the first pseudo variable heavy chain domain are intramolecularly linked to form an inactive Fv. The protein according to any one of claims 1 to 2, wherein the first variable heavy chain domain is the N terminus of the first variable light chain domain, and the pseudo light chain variable domain is the N terminus of the pseudo variable heavy chain domain. The protein according to any one of claims 1 to 2, wherein the first variable heavy chain domain is the N terminus of the first variable light chain domain, and the pseudo variable heavy chain domain is the N terminus of the pseudo variable light chain domain. The protein according to any one of claims 1 to 2, wherein the first variable light chain domain is the N terminal of the first variable heavy chain domain, and the pseudo light chain variable domain is the N terminal of the pseudo variable heavy chain domain. The protein according to any one of claims 1 to 2, wherein the first variable light chain domain is the N terminus of the first variable heavy chain domain, and the pseudo variable heavy chain domain is the N terminus of the pseudo variable light chain domain. The protein according to claim 1, wherein the first and second TTA are the same. The protein according to claim 1, wherein the first and second TTA are different. The protein of claim 1, wherein the first and second TTA are selected from EGFR, EpCAM, FOLR1 and B7H3. The method according to any one of claims 1 to 9, wherein the first and second sdABD-TTAs are SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21. , SEQ ID NO: 25, SEQ ID NO: 29; SEQ ID NO: 33; A protein selected from the group consisting of SEQ ID NO: 37 and SEQ ID NO: 41. The protein of any one of claims 1 to 10, wherein the half-life extending domain has SEQ ID NO: 45. The method according to any one of claims 1 to 11, wherein the cleavable linker is MMP2, MMP9, mephrine A, mephrine B, cathepsin S, cathepsin K, cathepsin L, granzyme B, uPA, kallikrein 7, Protein cleaved by a human protease selected from the group consisting of Matriptase and Thrombin. The method according to claim 1, Pro186, Pro225, Pro226, Pro233, Pro311, Pro312, Pro313, Pro495, Pro246, Pro254, Pro255, Pro256, Pro420, Pro421, Pro432, Pro479, Pro480, Pro187, Pro221, Pro222, Pro223, Pro224, Pro393 , Pro394, Pro395, Pro396, Pro429, Pro430 and Pro431, including proteins selected from the group consisting of proteins. A nucleic acid encoding a protein according to claim 1. An expression vector comprising the nucleic acid of claim 14. A host cell comprising the expression vector of claim 15. A method of making a protein, comprising culturing the host cell of claim 16 under conditions where the protein is expressed, and recovering the protein. A method of treating cancer, comprising administering the protein of any one of claims 1 to 13 to a patient. In a composition comprising:
a) from the N-terminal to the C-terminal, the first protein comprising:
i) the first sdABD-TTA;
ii) first domain linker;
iii) from the N-terminal to the C-terminal, a pseudo Fv domain comprising:
1) variable heavy chains including vhCDR1, vhCDR2 and vhCDR3;
2) cleavable linker; And
3) the first pseudo variable light domain comprising iVLCDR1, iVLCDR2 and iVLCDR3;
iv) second domain linker;
v) the first sdABD that binds human serum albumin;
a) from the N end to the C end, a second protein comprising:
i) a third sdABD binding to the human tumor target antigen;
ii) a third domain linker;
iii) from the N-terminal to the C-terminal, a pseudo Fv domain comprising:
1) variable light chains including VLCDR1, VLCDR2 and VLCDR3;
2) cleavable linker; And
3) the first pseudo variable heavy chain domain comprising iVHCDR1, iVHCDR2 and iVHCDR3;
iv) a fourth domain linker;
v) a fourth sdABD that binds human serum albumin;
here,
The first variable heavy chain domain and the first variable light chain domain are capable of binding human CD3 when associated;
The first variable heavy chain domain and the first pseudo variable light chain domain form inactive Fvs intermolecularly;
The first variable light chain domain and the first pseudo variable heavy chain domain form an inactive Fv in association with the molecule;
Wherein the first and third sdABD are SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 25, SEQ ID NO: 29; SEQ ID NO: 33; A composition selected from the group consisting of SEQ ID NO: 37 and SEQ ID NO: 41. The protein of claim 19, wherein the first and second TTA are the same. The protein of claim 19, wherein the first and second TTA are different. 22. The protein of any one of claims 19-21, wherein the third and fourth sdABDs have SEQ ID NO: 45. Nucleic acid composition comprising:
a) a first nucleic acid encoding the first protein according to any one of claims 19 to 22; And
b) A second nucleic acid encoding a second protein according to any one of claims 19 to 22. Expression vector composition comprising:
a) a first expression vector comprising the first nucleic acid of claim 23; And
b) A second expression vector comprising the second nucleic acid of claim 23. A host cell comprising the expression vector composition of claim 24. A method of making a composition, comprising culturing the host cell of claim 25 under conditions where the protein is expressed, and recovering the protein. A method of treating cancer, comprising administering to the patient the protein of any one of claims 19-22. In a composition comprising:
a) from the N-terminal to the C-terminal, the first protein comprising:
i) the first sdABD-TTA;
ii) first domain linker;
iii) a second sdABD-TTA;
iv) second domain linker;
iii) from the N-terminal to the C-terminal, a pseudo Fv domain comprising:
1) variable heavy chains including vhCDR1, vhCDR2 and vhCDR3;
2) cleavable linker; And
3) the first pseudo variable light domain comprising iVLCDR1, iVLCDR2 and iVLCDR3;
iv) a third domain linker; And
v) sdABD-HSA;
a) from the N end to the C end, a second protein comprising:
i) a third sdABD-TTA;
ii) a fourth domain linker;
iii) fourth sdABD-TTA;
iv) fifth domain linker;
iii) from the N-terminal to the C-terminal, a pseudo Fv domain comprising:
1) variable light chains including VLCDR1, VLCDR2 and VLCDR3;
2) cleavable linker; And
3) the first pseudo variable heavy chain domain comprising iVHCDR1, iVHCDR2 and iVHCDR3;
iv) sixth domain linker;
v) sdABD-HSA;
here,
The first variable heavy chain domain and the first variable light chain domain are capable of binding human CD3 when associated;
The first variable heavy chain domain and the first pseudo variable light chain domain form inactive Fvs intermolecularly;
The composition wherein the first variable light chain domain and the first pseudo variable heavy chain domain form inactive Fvs intermolecularly. 29. The composition of claim 28, wherein the sdABD-HSAs have SEQ ID NO: 45. Nucleic acid composition comprising:
a) a first nucleic acid encoding the first protein according to any one of claims 28 to 29; And
b) A second nucleic acid encoding a second protein according to any one of claims 28 to 29, respectively. Expression vector composition comprising:
a) a first expression vector comprising the first nucleic acid of claim 30; And
b) A second expression vector comprising the second nucleic acid of claim 30. A host cell comprising the expression vector composition of claim 31. A method of making a composition, comprising culturing the host cell of claim 32 under conditions where the protein is expressed, and recovering the protein. A method of treating cancer, comprising administering to the patient the protein of any one of claims 28-29. From N-terminus to C-terminus, for proteins comprising:
a) a single domain antigen binding domain (sdABD) (sdABD-TTA) that binds to human tumor target antigen (TTA);
b) the first domain linker;
c) Constrained Fv domain comprising:
i) the first variable heavy chain domain comprising vhCDR1, vhCDR2 and vhCDR3;
ii) Constrained Uncleavable Linker (CNCL); And
iii) the first variable light domain comprising vlCDR1, vlCDR2 and vlCDR3;
d) a cleavable linker (CL);
e) a second sdABD that binds human serum albumin;
f) domain linker;
g) Constrained caustic Fv domains comprising:
i) the first pseudo light chain variable domain;
ii) non-cleavable linker (NCL); And
iii) the first pseudo heavy chain variable domain;
Wherein the first variable heavy chain domain and the first variable light chain domain can bind human CD3, but the restricted Fv domain does not bind CD3;
The first variable heavy chain domain and the first pseudo variable light chain domain are intramolecularly linked to form an inactive Fv; And
The protein, wherein the first variable light chain domain and the first pseudo variable heavy chain domain are intramolecularly linked to form an inactive Fv. The protein of claim 35, wherein the first variable heavy chain domain is the N terminus of the first variable light chain domain, and the pseudo light chain variable domain is the N terminus of the pseudo variable heavy chain domain. The protein of claim 35, wherein the first variable heavy chain domain is the N terminus of the first variable light chain domain, and the pseudo variable heavy chain domain is the N terminus of the pseudo variable light chain domain. The protein of claim 35, wherein the first variable light chain domain is the N terminus of the first variable heavy chain domain, and the pseudo light chain variable domain is the N terminus of the pseudo variable heavy chain domain. 36. The protein of claim 35, wherein the first variable light chain domain is the N terminus of the first variable heavy chain domain, and the pseudo variable heavy chain domain is the N terminus of the pseudo variable light chain domain. The protein of claim 35, wherein the TTA is selected from EGFR, EpCAM, FOLR1 and B7H3. 41. The method of any one of claims 35-40, wherein the sdABD-TTA is SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 25 , SEQ ID NO: 29; SEQ ID NO: 33; A protein selected from the group consisting of SEQ ID NO: 37 and SEQ ID NO: 41. 42. The protein of any one of claims 35-41, wherein the half-life extending domain has SEQ ID NO: 45. The cleavable linker of any one of claims 35-42, wherein the cleavable linker is MMP2, MMP9, mephrine A, mephrine B, cathepsin S, cathepsin K, cathepsin L, granzyme B, uPA, kallikrein 7, Protein cleaved by a human protease selected from the group consisting of Matriptase and Thrombin. The protein of claim 35, comprising Pro258, Pro356, Pro359, Pro388 and Pro364. A nucleic acid encoding a protein according to claim 35. An expression vector comprising the nucleic acid of claim 45. A host cell comprising the expression vector of claim 46. A method of making a protein, comprising culturing the host cell of claim 47 under conditions where the protein is expressed, and recovering the protein. A method of treating cancer, comprising administering to the patient the protein of any one of claims 35-44.

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